84 results on '"Saper M"'
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2. Novel tertiary structures and stereospecificities of periplasmic binding proteins involved in active transport and chemotaxis
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Quiocho, F. A., Vyas, N. K., Pflugrath, J. W., Saper, M. A., Vyas, M. N., and Sack, J. S.
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- 1985
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3. Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis.
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Denu, J M, primary, Lohse, D L, additional, Vijayalakshmi, J, additional, Saper, M A, additional, and Dixon, J E, additional
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- 1996
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4. Structure of the human class I histocompatibility antigen, HLA-A2.
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Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C.
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- 1987
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5. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens.
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Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C.
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- 1987
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6. The X-ray crystal structures of Yersinia tyrosine phosphatase with bound tungstate and nitrate. Mechanistic implications.
- Author
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Fauman, E B, Yuvaniyama, C, Schubert, H L, Stuckey, J A, and Saper, M A
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X-ray crystal structures of the Yersinia tyrosine phosphatase (PTPase) in complex with tungstate and nitrate have been solved to 2. 4-A resolution. Tetrahedral tungstate, WO42-, is a competitive inhibitor of the enzyme and is isosteric with the substrate and product of the catalyzed reaction. Planar nitrate, NO3-, is isosteric with the PO3 moiety of a phosphotransfer transition state. The crystal structures of the Yersinia PTPase with and without ligands, together with biochemical data, permit modeling of key steps along the reaction pathway. These energy-minimized models are consistent with a general acid-catalyzed, in-line displacement of the phosphate moiety to Cys403 on the enzyme, followed by attack by a nucleophilic water molecule to release orthophosphate. This nucleophilic water molecule is identified in the crystal structure of the nitrate complex. The active site structure of the PTPase is compared to alkaline phosphatase, which employs a similar phosphomonoester hydrolysis mechanism. Both enzymes must stabilize charges at the nucleophile, the PO3 moiety of the transition state, and the leaving group. Both an associative (bond formation preceding bond cleavage) and a dissociative (bond cleavage preceding bond formation) mechanism were modeled, but a dissociative-like mechanism is favored for steric and chemical reasons. Since nearly all of the 47 invariant or highly conserved residues of the PTPase domain are clustered at the active site, we suggest that the mechanism postulated for the Yersinia enzyme is applicable to all the PTPases.
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- 1996
7. Leucine, isoleucine, valine-binding protein from Escherichia coli. Structure at 3.0-A resolution and location of the binding site.
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Saper, M A and Quiocho, F A
- Abstract
The structure of the leucine, isoleucine, valine-binding protein, an integral part of the high-affinity, branched-chain aliphatic amino acid transport system in Escherichia coli, has been solved at 3.0-A resolution by x-ray crystallography. Five isomorphous heavy atom derivatives, including anomalous differences from a samarium derivative, were used. A model of the polypeptide chain backbone reveals two distinct, globular domains connected by three strands. Each domain consists of a beta-sheet core flanked by at least two helices on either side. Difference Fourier analyses of crystals soaked in L-leucine, L-isoleucine, or L-valine have located a single amino acid-binding site in the cleft formed by the two domains. Despite the lack of significant sequence homology, the bilobate and secondary structure observed were similar to that found in the structures of L-arabinose- and D-galactose-binding proteins previously determined in our laboratory.
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- 1983
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8. The purification and characterization of a human dual-specific protein tyrosine phosphatase.
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Denu, J M, Zhou, G, Wu, L, Zhao, R, Yuvaniyama, J, Saper, M A, and Dixon, J E
- Abstract
An expression and purification method was developed to obtain the recombinant human dual-specific protein tyrosine phosphatase (PTPase) VHR in quantities suitable for both kinetic studies and crystallization. Physical characterization of the homogeneous recombinant protein verified the mass to be 20,500 +/- 100 by matrix-assisted laser desorption mass spectrometry, confirmed the anticipated NH2-terminal amino acid sequence and demonstrated that the protein exists as a monomer. Conditions were developed to obtain crystals which were suitable for x-ray structure determination. Using synthetic diphosphorylated peptides corresponding to MAP177-189 (mitogen-activated protein) kinase (DHTG-FLpTEpYVATR), an assay was devised which permitted the determination of the rate constants for dephosphorylation of the diphosphorylated peptide on threonine and tyrosine residues. The diphosphorylated peptides are preferred over the singly phosphorylated on tyrosine by 3-8-fold. The apparent second-order rate constant kcat/Km for dephosphorylation of phosphotyrosine on DHTGFLpTEpYVATR was 32,000 M-1 S-1 while dephosphorylation of phosphothreonine was 14 M-1 S-1 (pH 6). The reaction of DHTGFLpTEpYVATR with VHR is ordered, with rapid dephosphorylation on tyrosine occurring first followed by slow dephosphorylation on threonine. Similar results were obtained with F(NLe)(N-Le)pTPpYVVTR, a peptide corresponding to a MAP kinase-like protein (JNK1(180-189)) which is involved in the stress response signaling pathway.
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- 1995
9. The role of autoimmune t lymphocytes in the pathogenesis of multiple sclerosis
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Hohlfeld, R., Meinl, E., Weber, F., Zipp, F., Schmidt, S., Sotgiu, S., Goebels, N., Voltz, R., Spuler, S., Iglesias, A., Wekerle, H., Staudt, L. M., Lenardo, M. J., Matis, L. A., Germain, R. N., Margulies, D. H., Bjorkman, P. J., Saper, M. A., Samraoui, B., Brown, J. H., Jardetzky, T. S., Gorga, J. C., Ben-Nun, A., Cohen, I. R., Toyka, K. V., Heininger, K., Drexler, K., Fleckenstein, B., Allegretta, M., Nicklas, J. A., Sriram, S., Albertini, R. J., Ofosu-Appiah, W., Mokhtarian, F., Miller, A., Grob, D., Zhang, J., Markovic, S., Lacet, B., Oksenberg, J. R., Panzara, M. A., Begovich, A. B., Kojima, K., Lannes-Vieira, J., Lassmann, H., Fritz Zimprich, Rossler, K., Berger, T., Wucherpfennig, K. W., Weiner, H. L., Hafler, D. A., Martin, R., Mcfarland, H. F., Mcfarlin, D. E., Uematsu, Y., Wege, H., Straus, A., Salvetti, M., Ristori, G., D Amato, M., Witek, C., Selmaj, K., Brosnan, C. F., Raine, C. S., Battistini, L., Kowal, C., Arnason, B. G. W., Steinman, L., Medaer, R., Stinissen, P., Bourdette, D. N., Whitham, R. H., Chou, Y. K., and Friedman, A.
10. Structure of leucine, isoleucine, valine-binding protein fromE. coliat 2.8 Å resolution
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Saper, M. A., primary and Quiocho, F. A., additional
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- 1984
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11. Specificity pockets for the side chains of peptide antigens in HLA-Aw68
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Garrett, T. P. J., primary, Saper, M. A., additional, Bjorkman, P. J., additional, Strominger, J. L., additional, and Wiley, D. C., additional
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- 1989
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12. Structures of several binding proteins involved in active transport and chemotaxis
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Quiocho, F. A., primary, Vyas, N. K., additional, Pflugrath, J. W., additional, Saper, M. A., additional, and Vyas, M. N., additional
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- 1984
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13. Crystallization and preliminary X-ray diffraction studies of the lectin from
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SAPER, M
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- 1987
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14. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 p resolution
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SAPER, M
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- 1991
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15. Crystallization of a DNA tridecamer d(C-G-C-A-G-A-A-T-T-C-G-C-G)
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SAPER, M
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- 1986
16. The 2.2 Angstrom Crystal Structure of Hsp33: A Heat Shock Protein with Redox-Regulated Chaperone Activity
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Saper, M
- Published
- 2001
17. MRI Features That Contribute to Decision-Making for Treatment of Capitellar OCD Lesions: An Expert Consensus Using the Delphi Method.
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Kostyun RO, Nguyen JC, Chhabra B, Todd R Lawrence J, Polousky JD, Saper M, Uquillas C, Nissen CW, Kostyun RO, Albright J, Bae D, Bohn D, Chan C, Crepeau A, Edmonds E, Fabricant P, Ganley T, Little K, Lee Pace J, Pacicca D, Pennock A, Saluan P, Shea K, Wall E, Wilson P, and Nissen CW
- Abstract
Background: Most healthcare providers utilize magnetic resonance imaging (MRI) to assist in diagnosing and treating osteochondritis dissecans (OCD) of the capitellum. However, consensus on imaging features that portend clinically relevant information in the care of these lesions has not been determined., Purpose: To conduct a survey on the MRI features of a capitellar OCD that are salient for clinical decision-making using a classic Delphi protocol., Study Design: A consensus statement., Methods: Invitations to participate were sent to 33 healthcare providers identified as capitellar OCD experts. A classic 3-round survey method was used to gather agreement and consensus on the level of importance for clinical decision-making on 33 MRI features. A concise list of features that guide decision-making on the stability of an OCD lesion and the ability of an OCD lesion to heal with nonoperative care was also identified. Agreement and consensus were determined a priori as ≥66%., Results: Of the 33 identified experts, 20 agreed to participate, and 17 (52%) completed all 3 rounds. Of the 33 MRI features evaluated, 17 reached agreement as important for clinical decision-making by the experts. Consensus was reached for a concise list of MRI features that were significant to decision-making (94%), suggestive of a stable lesion (100%), had the potential to heal with nonoperative treatment (94%), were suggestive of an unstable lesion (100%), and had low potential to heal with nonoperative treatment (88%)., Conclusion: This 3-round Delphi process produced consensus on clinically relevant MRI features that contribute to clinical decision-making for capitellar OCD. The results of this study will be used as the basis for an interrater reliability assessment of the identified salient features, creating the foundation for developing a reliable MRI assessment tool rooted in clinical experiences. The development of a standardized assessment of capitellar OCD is intended to improve clinical practice and patient outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.A. has received research funds from Smith+ Nephew. J.D.P. has received education payments from Rock Medical Orthopedics and Pylant Medical. D.B. has received royalties from Lippincott Williams & Wilkins. E.E. has received nonconsulting fees from Arthrex. T.G. has received research support from Vericel and AlloSource; education payments from Arthrex; and is a paid associate editor for The American Journal of Sports Medicine. J.L.P. has received consulting fees from Arthrex and JRF Ortho. D.P. has received education payments from Arthrex and has stock ownership in Zimmer Biomet, Medtronic, and Walgreens. P.S. has received speaking fees from Arthrex. M.S. has received grant support from DJO; education payments from Arthrex and Smith+Nephew; and nonconsulting fees from Arthrex. K.S. has received research grants from RCT and Vericel; education payments from Evolution Inc, Arthrex, and Stryker; and hospitality payments from BioMarin Pharmaceutical. E.W. has received education payments from Legacy Ortho. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from Hartford HealthCare (ref No. HHC-2022-0182)., (© The Author(s) 2024.)
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- 2024
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18. Comparison of physical therapy utilization, timing of return-to-sport test completion, and hop test performance by age and between sexes in youth athletes after anterior cruciate ligament reconstruction.
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Butler L, Greenberg E, Giampetruzzi N, Link M, Prati V, Weaver A, and Saper M
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- Humans, Male, Adolescent, Female, Retrospective Studies, Sex Factors, Age Factors, Time Factors, Athletes, Athletic Injuries surgery, Athletic Injuries rehabilitation, Anterior Cruciate Ligament Reconstruction rehabilitation, Return to Sport, Exercise Test, Physical Therapy Modalities, Anterior Cruciate Ligament Injuries surgery, Anterior Cruciate Ligament Injuries rehabilitation
- Abstract
Objective: To compare physical therapy (PT) utilization, timing of return-to-sport (RTS) test and hop test performance by age and between sexes in youth after anterior cruciate ligament reconstruction (ACLR)., Design: Multicenter retrospective cohort., Methods: A retrospective review of adolescents after primary ACLR was conducted. Participants completed return-to-sport (RTS) tests including single-legged hop testing. PT frequency, average weekly visits, and timing of RTS test were calculated. T-tests assessed the effect of age and sex on average weekly PT visits and multivariable logistic regressions assessed odds of passing hop tests., Results: 289 participants were included (15.7 ± 1.9 years). There was no difference in average weekly PT visits (p = 0.321) or time to RTS test (p = 0.162) by age. There were significant differences in average weekly PT visits (p = 0.047) and mean time from surgery to RTS test (p = 0.048) between sexes with small effect sizes (d = 0.24 and d = 0.21, respectively). Age and sex had no effect on odds of passing hop tests (OR, 1.29; 95% CI, 0.71-2.35 and OR, 0.79; 95%CI, 0.43-1.45, respectively)., Conclusion: In a youth cohort, age and sex may have no clinically important effect on PT visit utilization, timing of RTS test or hop test performance., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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19. Effect of Age and Body Mass Index on Time to Advanced Imaging and Surgery in Young Athletes With Anterior Cruciate Ligament Injury.
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Sliepka JM, Gatto J, Iyer A, Saper M, Schmale G, Gee A, Kweon C, Chin K, and Hagen M
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Background: In young athletes with anterior cruciate ligament (ACL) injury, increased times from injury to magnetic resonance imaging (MRI) and injury to surgery can lead to the accrual of new injuries over time., Purpose: To determine the patient characteristics associated with differences in timing between injury, MRI, and surgery in young athletes with ACL tears., Study Design: Case-control study; Level of evidence, 3., Methods: We reviewed the electronic medical records of patients aged 13 to 25 years who underwent isolated primary ACL reconstruction between January 2017 and June 2020 at a single orthopaedic surgery department. The times from injury to MRI, MRI to surgery, and injury to surgery were documented. Patient demographic data (age, sex, body mass index [BMI], race and ethnicity, and insurance type) were recorded. Multivariable analysis was used to determine if any patient characteristic had a significant association with increased time to MRI or surgery., Results: A total of 369 patients (mean age, 18.0 years; 56% female) were included. Both age and BMI were found to be significantly associated with timing of care while holding all other predictors constant. For every 1-year increase in patient age, time from injury to MRI increased by 9.6 days (95% CI, 1.8-17.4 days; P = .02), time from MRI to surgery increased by 7.4 days (95% CI, 4.4-10.5 days; P < .001), and time from injury to surgery increased by 17.0 days (95% CI, 8.4-25.6 days; P < .001). Compared with patients with normal BMI, overweight patients (BMI range, 25-29.9 kg/m
2 ) had an MRI-to-surgery time that was on average 37.2 days (95% CI, 11.7-62.7 days; P < .004) longer and an injury to surgery time that was on average 71.8 days (95% CI, 0.5-143.0 days; P = .048) longer. Obese patients (BMI ≥30 kg/m2 ) did not demonstrate a significant relationship with the studied time intervals., Conclusion: Increasing age and elevated BMI were found to be associated with increased time to MRI and surgical care in young athletes with ACL injuries., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.S. has received education payments from Summit Surgical and Arthrex and nonconsulting fees from Arthrex. G.S. has received education payments from Summit Surgical. A.G. has received education payments from Summit Surgical, Smith & Nephew, and Miach Orthopaedics and hospitality payments from Arthrex and Zimmer Biomet Holdings. C.K. has received education payments from Summit Surgical and Smith & Nephew and hospitality payments from Arthrex. K.C. has received education payments from Summit Surgical and Arthrex and hospitality payments from Stryker. M.H. has received education payments from Smith & Nephew, Summit Surgical, and Arthrex; consulting fees from Smith & Nephew and Linvatec; and hospitality payments from RTI Surgical and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from University of Washington (ref No. STUDY00009903)., (© The Author(s) 2024.)- Published
- 2024
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20. Relationship Between Age and Pathology With Treatment of Pediatric and Adolescent Discoid Lateral Meniscus: A Report From the SCORE Multicenter Database.
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Silverstein RS, McKay SD, Coello P, Pupa L, Latz K, Craig Kemper W, Adsit E, Wilson PL, Albright J, Algan S, Beck J, Bowen RE, Brey J, Marc Cardelia J, Clark C, Crepeau A, Edmonds E, Ellington M, Fabricant PD, Frank JS, Ganley TJ, Green DW, Gupta A, Heyworth B, Mansour A, Mayer S, Milewski MD, Niu E, Pacicca DM, Parikh SN, Rhodes J, Saper M, Schmale GA, Schmitz M, Shea K, Storer S, and Ellis HB Jr
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- Humans, Child, Adolescent, Menisci, Tibial surgery, Menisci, Tibial pathology, Cohort Studies, Arthroscopy methods, Retrospective Studies, Tibial Meniscus Injuries surgery, Joint Diseases surgery, Cartilage Diseases
- Abstract
Background: Surgical treatment options of discoid lateral meniscus in pediatric patients consist of saucerization with or without meniscal repair, meniscocapular stabilization, and, less often, subtotal meniscectomy., Purpose: To describe a large, prospectively collected multicenter cohort of discoid menisci undergoing surgical intervention, and further investigate corresponding treatment of discoid menisci., Study Design: Cohort study; Level of evidence, 3., Methods: A multicenter quality improvement registry (16 institutions, 26 surgeons), Sports Cohort Outcomes Registry, was queried. Patient characteristics, discoid type, presence and type of intrasubstance meniscal tear, peripheral rim instability, repair technique, and partial meniscectomy/debridement beyond saucerization were reviewed. Discoid meniscus characteristics were compared between age groups (<14 and >14 years old), based on receiver operating characteristic curve, and discoid morphology (complete and incomplete)., Results: In total, 274 patients were identified (mean age, 12.4 years; range, 3-18 years), of whom 55.6% had complete discoid. Meniscal repairs were performed in 55.1% of patients. Overall, 48.5% of patients had rim instability and 36.8% had >1 location of peripheral rim instability. Of the patients, 21.5% underwent meniscal debridement beyond saucerization, with 8.4% undergoing a subtotal meniscectomy. Patients <14 years of age were more likely to have a complete discoid meniscus ( P < .001), peripheral rim instability ( P = .005), and longitudinal tears ( P = .015) and require a meniscal repair ( P < .001). Patients ≥14 years of age were more likely to have a radial/oblique tear ( P = .015) and require additional debridement beyond the physiologic rim ( P = .003). Overall, 70% of patients <14 years of age were found to have a complete discoid meniscus necessitating saucerization, and >50% in this young age group required peripheral stabilization/repair., Conclusion: To preserve physiological "normal" meniscus, a repair may be indicated in >50% of patients <14 years of age but occurred in <50% of those >14 years. Additional resection beyond the physiological rim may be needed in 15% of younger patients and 30% of those aged >14 years., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: See the Appendix (available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
- Published
- 2023
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21. Age, Sex, and BMI Differences Related to Repairable Meniscal Tears in Pediatric and Adolescent Patients.
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Rohde MS, Shea KG, Dawson T 2nd, Heyworth BE, Milewski MD, Edmonds EW, Adsit E, Wilson PL, Albright J, Algan S, Beck J, Bowen R, Brey J, Cardelia M, Clark C, Crepeau A, Edmonds EW, Ellington M, Ellis HB, Fabricant P, Frank J, Ganley T, Green D, Gupta A, Heyworth BE, Latz K, Mansour A, Mayer S, McKay S, Milewski M, Niu E, Pacicca D, Parikh S, Rhodes J, Saper M, Schmale G, Schmitz M, Shea K, Storer S, Wilson PL, and Ellis HB
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- Humans, Male, Adolescent, Female, Child, Body Mass Index, Anterior Cruciate Ligament surgery, Prospective Studies, Retrospective Studies, Menisci, Tibial surgery, Rupture surgery, Arthroscopy methods, Knee Injuries surgery, Anterior Cruciate Ligament Injuries surgery, Lacerations
- Abstract
Background: The incidence of meniscus tears and ACL tears in pediatric patients continues to rise, bringing to question the risk factors associated with these injuries. As meniscus tears are commonly repaired in pediatric populations, the epidemiology of repairable meniscus tears is an important for consideration for surgeons evaluating treatment options., Purpose: To describe meniscal tear patterns in pediatric and adolescent patients who underwent meniscal repair across multiple institutions and surgeons, as well as to evaluate the relationship between age, sex, and body mass index (BMI) and their effect on the prevalence, type, and displacement of repaired pediatric meniscal tears., Study Design: Case series; Level of evidence, 4., Methods: Data within a prospective multicenter cohort registry for quality improvement, Sport Cohort Outcome Registry (SCORE), were reviewed to describe repaired meniscal tear patterns. All consecutive arthroscopic meniscal repairs from participating surgeons in patients aged <19 years were analyzed. Tear pattern, location, and displacement were evaluated by patient age, sex, and BMI. A subanalysis was also performed to investigate whether meniscal tear patterns differed between those occurring in isolation or those occurring with a concomitant anterior cruciate ligament (ACL) injury. Analysis of variance was used to generate a multivariate analysis of specified variables. Sex, age, and BMI results were compared across the cohort., Results: There were 1185 total meniscal repairs evaluated in as many patients, which included 656 (55.4%) male and 529 (44.6%) female patients. Patients underwent surgery at a mean age of 15.3 years (range, 5-19 years), with a mean BMI of 24.9 (range, 12.3-46.42). Of the 1185 patients, 816 (68.9%) had ACL + meniscal repair and 369 (31.1%) had isolated meniscal repair. The male patients underwent more lateral tear repairs than the female patients (54.3% to 40.9%; P < .001) and had a lower incidence of medial tear repair (32.1% vs 41.4%; P < .001). Patients with repaired lateral tears had a mean age of 15.0 years, compared with a mean age of 15.4 years for patients with repaired medial or bilateral tears ( P = .001). Higher BMI was associated with "complex" and "radial" tear repairs of the lateral meniscus ( P < .001) but was variable with regard to medial tear repairs., Conclusion: In pediatric and adolescent populations, the data suggest that the surgical team treating knees with potential meniscal injury should be prepared to encounter more complex meniscal tears, commonly indicated in those with higher BMI, while higher rates of lateral meniscal tears were seen in male and younger patients. Future studies should analyze correlates for meniscal repair survival and outcomes in this pediatric cohort undergoing knee surgery.
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- 2023
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22. A Corresponding Point Measurement System Provides Reliable Measurement of Displacement for Medial Epicondyle Fractures.
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Guzek RH, Harwood K, Isaacs D, Talwar D, Edmonds EW, Fabricant PD, Joughin VE, Latz KH, Mayer SW, McKay S, Pacicca DM, Saper M, and Lawrence JTR
- Abstract
Little consensus exists on the best method for evaluation and management of pediatric medial epicondyle fractures because of an inability to reliably evaluate fracture displacement with standard imaging techniques. This study aimed to determine the performance of various radiographic views in evaluating displaced medial epicondyle fractures when using a standardized measurement methodology., Methods: Ten fellowship-trained pediatric orthopaedic surgeons assessed fracture displacement in 6 patients with displaced medial epicondyle fractures using radiographic views (anteroposterior, lateral, axial, internal oblique [IO], and external oblique [EO]) and computed tomographic (CT) views (axial, 3-dimensional [3D] horizontal, and 3D vertical). Raters used a corresponding point method for measuring displacement. For each image, raters measured the absolute displacement, categorized the percent of displacement relative to the size of the fragment and fracture bed, and indicated a treatment option. Interobserver reliability was calculated for each view. Bland-Altman plots were constructed to evaluate the bias between each radiograph and the mean of the CT methods., Results: For absolute displacement, anteroposterior and EO views showed almost perfect interobserver reliability, with an interclass correlation coefficient (ICC) of 0.944 for the anteroposterior view and an ICC of 0.975 for the EO view. The axial view showed substantial reliability (ICC = 0.775). For the displacement category, almost perfect reliability was shown for the anteroposterior view (ICC = 0.821), the axial view (ICC = 0.911), the EO view (ICC = 0.869), and the IO view (ICC = 0.871). Displacement measurements from the anteroposterior, axial, and EO views corresponded to the measurements from the CT views with a mean bias of <1 mm for each view. However, the upper and lower limits of agreement were >5 mm for all views, indicating a substantial discrepancy between radiographic and CT assessments. Treatment recommendations based on CT changed relative to the recommendation made using the anteroposterior view 29% of the time, the EO view 41% of the time, and the axial view 47% of the time., Conclusions: Using a corresponding point measurement system, surgeons can reliably measure and categorize fracture displacement using anteroposterior, EO, and axial radiographic views. CT-based measurements are also reliable. However, although the mean difference between the radiograph-based measurements and the CT-based measurements was only about 1 mm, the discrepancy between radiographic views and CT-based methods could be as large as 5 to 6 mm., Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A438)., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)
- Published
- 2022
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23. Differences in the course of rehabilitation and outcomes for publicly insured pediatric patients after anterior cruciate ligament reconstruction.
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Greenberg E, Butler L, Giampetruzzi N, Link M, Prati V, Weaver A, and Saper M
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- Adolescent, Humans, Female, Child, Male, Retrospective Studies, Medicaid, Physical Therapy Modalities, Anterior Cruciate Ligament Injuries surgery, Anterior Cruciate Ligament Reconstruction rehabilitation
- Abstract
Objective: Examine the effect of insurance type on physical therapy (PT) utilization and outcomes within pediatric and adolescent patients after anterior cruciate ligament reconstruction., Design: Multicenter retrospective cohort study., Methods: PT visits and functional hop test performance were extracted into a shared database. The average number of PT visits per week was assessed overall and by time period. Independent samples t-test examined the effect of insurance on PT utilization and the effect of insurance status on the odds of passing single-legged hop tests was assessed using multivariable logistic regression., Results: A total of 281 patients (15.7 ± 1.9, 42% female) were included in this analysis. Of these, 128 (45%) had public insurance. Publicly insured patients experienced a longer delay from surgery to hop test (8.3vs7.7 months, p = 0.009), attended overall fewer PT visits per week (0.92vs1.04, p = 0.005), with most of the decreased frequency occurring between weeks 7-24. Insurance status had a significant effect on the odds of passing the single leg hop test (2.72; 95%CI, 1.27-5.81)., Conclusion: Publicly insured patients average a lower number of weekly PT visits, experienced a longer delay from surgery to hop testing and were 2.7 times less likely to pass the single leg hop for distance test., Competing Interests: Declaration of competing interest We, the authors, affirm that we have no financial or commercial affiliations related to the performance or outcome of this manuscript., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2022
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24. Adolescent Baseball Pitchers With Ulnar Collateral Ligament Tears Exhibit a High Proportion of Partial Tears.
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Goodrich E, Cox B, Plummer HA, Cohen A, Andrews JR, and Saper M
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- Adolescent, Cross-Sectional Studies, Humans, Retrospective Studies, Baseball, Collateral Ligament, Ulnar diagnostic imaging, Collateral Ligaments pathology, Elbow Joint diagnostic imaging
- Abstract
Background: Ulnar collateral ligament (UCL) tears in the throwing elbow are classified according to grade and location using magnetic resonance arthrography (MRA). However, the frequency of each tear type and the association to age, competition level, and radiographic findings in adolescent baseball pitchers are unknown., Purposes: The primary purpose of this study was to use MRA to characterize the severity, location, and UCL tear type in adolescent pitchers. The second aim was to describe the relationship between the UCL tear type and age, competition level, and plain radiographic findings., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Records of adolescent pitchers with a UCL tear treated by the senior author between 2007 and 2016 were retrospectively reviewed. MRA scans were reviewed and tears were classified according to the Joyner-Andrews classification. Low-grade partial tears are classified as type I, high-grade partial tears as type II, complete full-thickness tears as type III, and tear pathology in >1 region in the UCL as type IV. Each type of tear also has a location designated at the midsubstance, ulna (U), or humerus (H). Patient characteristics, competition level, and associated plain radiographic abnormalities were recorded. Univariate analyses were performed to examine the relationships between tear types and age, competition level, and plain radiographic findings., Results: A total of 200 adolescent pitchers (mean ± SD age, 17.2 ± 1.5 years) with MRA scans were reviewed. Type II-H (n = 62), type II-U (n = 51), and type III-U (n = 28) were the most common tear types observed. Type II tears comprised 64.5% of adolescent UCL tears, with type II-H being the most common. Plain radiographs were abnormal in 32% of patients, with calcifications (10.5%) and olecranon osteophytes (12.5%) being the most common findings. There were no significant relationships between tear type and age ( P = .25), competition level ( P = .23), or radiographic abnormalities ( P = .75)., Conclusion: Humeral-sided high-grade partial tears were the most common tear type in adolescent pitchers. There was no relationship between UCL tear type and age competition level, and plain radiographic abnormalities.
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- 2022
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25. Adolescent Patients Exhibit Significant Improvements in Strength and Functional Performance From 6 to 9 Months After ACL Reconstruction With Quadriceps Autograft.
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Saper M, Wong C, and Strauss N
- Abstract
Purpose: To investigate differences between the 6-month and 9-month return to sport (RTS) assessments in adolescent patients undergoing anterior cruciate ligament reconstruction (ACLR) with quadriceps tendon autograft., Methods: A retrospective review was performed of consecutive adolescent patients who underwent ACLR between June 2017 and October 2019. Patients completed a structured RTS test 6 and 9 months after surgery consisting of isometric and isokinetic strength testing, the Lower Quarter Y-Balance Test, and single-legged hop testing. The recovery of muscle strength, assessed via isometric/isokinetic and hop testing, was defined by a limb symmetry index (LSI) ≥90%. Differences were compared between the 2 RTS test time points., Results: In total, 27 patients (16 female, 11 male) were identified with a mean age of 15 years (range, 13-17 years). There were statistically significant improvements in isometric quadriceps strength (LSI, 85.0 ± 17.2 vs 92.5 ± 11.3; P = .04) and hamstring strength (LSI, 87.9 ± 11.2 vs 99.0 ± 10.5; P < .01). There were improvements in isokinetic knee extension at both 60°/s (LSI, 75.2 ± 16.7 vs 83.3 ± 13.8) and 180°/s (LSI, 79.9 ± 15.4 vs 83.4 ± 11.2), but the differences were only statistically significant at 60°/s ( P = .02 and P = .17, respectively). There were no significant differences in isokinetic testing of knee flexion at either 60°/s or 180°/s. There were no statistically significant differences in the anterior reach component of the Lower Quarter Y-Balance Test at 6 and 9 months. Patients demonstrated statistically significant improvements on single- legged hop testing with mean LSIs >95% for each of the 4 tests at 9 months postop., Conclusions: Adolescent patients undergoing ACLR with quadriceps tendon autograft demonstrated significant improvements in quadriceps strength between 6 and 9 months postoperatively., Level of Evidence: Level IV, therapeutic case series., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)
- Published
- 2021
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26. Effects of a Simulated Game on Upper Extremity Pitching Mechanics and Muscle Activations Among Various Pitch Types in Youth Baseball Pitchers.
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Oliver GD, Plummer H, Henning L, Saper M, Glimer G, Brambeck A, and Andrews JR
- Subjects
- Adolescent, Biomechanical Phenomena, Humans, Male, Baseball physiology, Electromyography methods, Muscle, Skeletal physiology, Scapula physiology, Shoulder Joint physiology, Upper Extremity physiology
- Abstract
Background: Throwing requires proper stability and orientation of the pelvis and scapula for efficient energy transfer during pitching. Fatigue of the pelvis and scapular musculature throughout the course of a game can impair pitching performance, and place excessive demands on the throwing arm leading to injury. The purpose of this study was to examine differences in pelvis, torso, and upper extremity pitching mechanics and muscle activations between the fastball, change-up, and curveball pitches in youth baseball pitchers following a simulated game., Methods: Fourteen youth baseball pitchers with no history of injury participated. Pitching mechanics were collected using an electromagnetic tracking system. Surface electromyography data were collected on the bilateral gluteus medius and maximus; and throwing arm side latissimus dorsi, lower trapezius, upper trapezius, and serratus anterior. Participants were instructed to throw maximum effort pitches during a simulated game that provided random game situations similar to those that occur in competition. Participants were limited to 85 pitches based on age-restricted pitch counts. Data from 3 fastballs, curveballs, and change-ups thrown in the first and last innings were selected for analysis., Results: Repeated measures multivariate analyses of variance revealed that neither pitch type nor the effect of a simulated game resulted in statistically significant changes in pitching mechanics (F(10,600)=0.55, P=0.85), or muscle activations (pelvic: F(4,195)=0.07, P=0.85; scapular: F(4,118)=0.09, P=0.52)., Conclusions: The principle findings of this study revealed that pitching to the age-restricted pitch count limit did not result in altered pitching mechanics or muscle activations, and no differences occurred between the 3 pitches. These results support previous research that indicate the curveball pitch is no more dangerous for youth than the other pitches commonly thrown. This is supported by the pitcher's ability to maintain a proper arm slot during all 3 pitches and indicates that they are obtaining the spin on the ball from their grip and not by altering upper extremity mechanics., Level of Evidence: Level 5.
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- 2019
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27. Minimizing Graft-Tunnel Mismatch in Allograft Anterior Cruciate Ligament Reconstruction Using Blumensaat's Line: A Cadaveric Study.
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Meijer K, Saper M, Joyner P, Liu W, Andrews JR, and Roth C
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- Adult, Aged, Allografts, Anterior Cruciate Ligament diagnostic imaging, Cadaver, Female, Humans, Male, Middle Aged, Radiography, Anterior Cruciate Ligament surgery, Anterior Cruciate Ligament Reconstruction methods, Femur surgery, Patellar Ligament transplantation, Tibia surgery
- Abstract
Purpose: To evaluate the accuracy of Blumensaat's line (BL) in predicting the tendinous graft length and tibial tunnel length (TTL) in an independent-tunnel anterior cruciate ligament reconstruction (ACLR) using a bone-patellar tendon-bone (BTB) allograft., Methods: Eighteen ACLRs were performed on cadaveric specimens using an anteromedial portal technique. All knees had no previous surgeries or deformities. Lateral knee radiographs of each specimen were taken prior to the ACLR, and BL was measured. Length-specific allografts for the tendinous portion of the grafts were then ordered by adding 20 mm to the length of BL. The TTL was predicted by subtracting BL and femoral tunnel length (FTL) from the overall graft length. Graft-tunnel mismatch (GTM) was recorded for each specimen. Statistical analysis compared overall results with the gold standard (0 mm) of GTM., Results: The average lateral femoral condyle width measured in line with the femoral tunnel was 33 ± 3.43 mm. The average FTL was 25 ± 0.54 mm. The average intra-articular distance (IAD) between femoral and tibial tunnel apertures was 31 ± 3.65 mm. The average TTL was 35 ± 2.21 mm. The difference between the predicted TTL and the actual TTL was not statistically significant (P = .3). The mean GTM was -0.9 ± 3.15 mm. There was no statistically significant difference between the BL method and the gold standard (P = .45). The mean percent difference between BL and the IAD was 5.2%., Conclusions: The BL method can accurately predict the desired length for the tendinous portion of a BTB allograft as well as the TTL, thereby potentially minimizing GTM during arthroscopic BTB allograft ACLR. Patient-specific allografts can be ordered preoperatively based on BL., Clinical Relevance: This method provides the surgeon a way to avoid GTM preoperatively by ordering patient-specific grafts prior to performing an independent-tunnel BTB allograft ACLR., (Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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28. Outcomes and Return to Sport After Ulnar Collateral Ligament Reconstruction in Adolescent Baseball Players.
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Saper M, Shung J, Pearce S, Bompadre V, and Andrews JR
- Abstract
Background: The number of ulnar collateral ligament (UCL) reconstructions in adolescent athletes has increased over the past 2 decades. Clinical results in this population have not been well studied., Purpose/hypothesis: The purpose of this study was to evaluate the outcomes and return to sport after UCL reconstruction in a large group of adolescent baseball players. We hypothesized that excellent clinical outcomes and high rates of return to sport would be observed in this population at a minimum 2-year follow-up., Study Design: Case series; Level of evidence, 4., Methods: We reviewed 140 adolescent (aged ≤19 years) baseball players who underwent UCL reconstruction with the American Sports Medicine Institute (ASMI) technique by a single surgeon. Medical records were reviewed for patient demographics, injury characteristics, operative details, and surgical complications. Patient-reported outcomes were assessed using the Conway scale, the Andrews-Timmerman (A-T) score, the Kerlan-Jobe Orthopaedic Clinic (KJOC) score, and a 0- to 100-point subjective scale for elbow function and satisfaction. Return to sporting activity was assessed using a custom-designed questionnaire., Results: The mean age at the time of surgery was 18.0 years (range, 13-19 years), and the mean follow-up was 57.9 months (range, 32.4-115.4 months). Over half (60%) of patients were high school athletes. The mean duration of symptoms before surgery was 6.9 months (range, 0.5-60.0 months). Partial tears were identified in 57.9% of patients, and 41.3% of patients had preoperative ulnar nerve symptoms. Graft type included the ipsilateral palmaris in 77.1% of patients. Concomitant procedures were performed in 25% of patients. Outcomes on the Conway scale were "excellent" in 86.4% of patients. The mean A-T and KJOC scores were 97.3 ± 6.1 and 85.2 ± 14.6, respectively. Mean patient satisfaction was 94.4. Overall, 97.8% of patients reported returning to sport at a mean of 11.6 months (range, 5-24 months), and 89.9% of patients returned to sport at the same level of competition or higher. A total of 11.6% of patients went on to play professional baseball., Conclusion: UCL reconstruction with the ASMI technique is an effective surgical option in adolescents, with excellent outcome scores. At a minimum of 2-year follow-up, nearly 90% of patients returned to their preinjury level of sport., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.S. has received educational support from Arthrex and Smith & Nephew and has received grants for fellowship training from DJO. J.R.A. is a consultant for Arthrex and Halyard Health and receives educational support from Smith & Nephew.
- Published
- 2018
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29. Outcomes and Return to Sport After Revision Anterior Cruciate Ligament Reconstruction in Adolescent Athletes.
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Saper M, Pearce S, Shung J, Zondervan R, Ostrander R, and Andrews JR
- Abstract
Background: The number of adolescent anterior cruciate ligament (ACL) injuries is rising with increased participation in higher level athletics at earlier ages. With an increasing number of primary ACL reconstructions (ACLRs) comes a rise in the incidence of revision ACLRs., Purpose: To evaluate the clinical results of revision ACLR across a group of high-level adolescent athletes with at least 2-year follow-up., Study Design: Case series; Level of evidence, 4., Methods: A retrospective review of 21 adolescent athletes (age range, 10-19 years) who underwent revision ACLR with at least 2-year follow-up was conducted. Patient-reported outcome measures (PROMs) included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Lysholm knee scoring scale, Tegner activity level scale, and modified Cincinnati Knee Rating System. Return to sport (RTS) and overall patient satisfaction were also assessed., Results: The mean age at the time of surgery was 16.5 years (range, 14-19 years), and the mean follow-up was 46.4 months (range, 24-97 months); 42.9% of patients were female, and 52.4% of patients participated in collision sports. The mean time to failure after primary ACLR was 13.1 ± 8.0 months, and the most common mechanism of failure was noncontact in at least 66.7% of cases. The revision graft type included bone-patellar tendon-bone (BPTB) in 71.4% of cases; 26.7% of BPTB grafts were from the contralateral extremity. Concomitant procedures were performed for intra-articular lesions in 71.4% of patients. The mean patient satisfaction rate was 95.3%. There were 3 cases of a graft reinjury at a mean of 25 months postoperatively. The mean PROM scores were as follows: IKDC, 87.5 ± 12.7; Tegner, 7.2 ± 2.0; Lysholm, 93.7 ± 9.8; and Cincinnati, 93.4 ± 10.0. Of those attempting to RTS, 68.4% of patients successfully returned at the same level of competition. Patients with a lateral compartment chondral injury were less likely to RTS ( P < .05). Independent variables shown to have no significant relationship to PROMs or RTS included age, follow-up, sport classification, associated meniscal tears, revision graft size/type, and concomitant procedures., Conclusion: Revision ACLR can be an effective surgical option in adolescents participating in collision and contact sports, with good to excellent subjective outcome scores. At a minimum 2-year follow-up, a graft rupture after revision ACLR occurred in 14% of cases. Of the athletes attempting to RTS, 68.4% returned to their preinjury level of competition., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.S. has received educational support from Arthrex and Smith & Nephew and has received grant support for fellowship training from DJO Global. R.O. is a consultant for DePuy Synthes and Halyard Health, has received honoraria from Halyard Health, and has received hospitality payments from Halyard Health. J.R.A. is a consultant for Arthrex and Halyard Health, has received educational support from Smith & Nephew, and has received hospitality payments from Arthrex.
- Published
- 2018
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30. Lateral Patellofemoral Ligament Reconstruction With a Gracilis Allograft.
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Saper M
- Abstract
Isolated medial patellar subluxation (MPS), in the absence of a previous lateral retinacular release, is a poorly recognized clinical condition characterized by chronic anterior knee pain that is exacerbated with knee flexion. This type of patellar instability is often overlooked, and a high index of suspicion is needed for appropriate diagnosis and treatment. The purpose of this Technical Note is to describe a surgical technique to reconstruct the lateral patellofemoral ligament with an allograft gracilis tendon. By restoring stability to the lateral side of the patella, this minimally invasive technique successfully treats cases of isolated MPS.
- Published
- 2018
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31. Clinical results after treatment for bidirectional patellar subluxation: Minimum 2-years follow-up.
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Saper M, Brady C, Zondervan R, and Shneider D
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Male, Middle Aged, Patient Satisfaction, Recovery of Function, Time Factors, Treatment Outcome, Young Adult, Patellar Dislocation surgery
- Abstract
Background: We describe the preliminary clinical results of a patellar stabilization technique to treat bidirectional patellar subluxation (BPS)., Methods: Patients: six patients (one male, five females; mean age 30.2years) underwent this procedure with a minimum of 24months follow-up. Patients were assessed for clinical instability, patellar complications, and need for revision surgery. Patient functional outcomes were evaluated using the criteria of Crosby and Insall and the Kujala Anterior Knee Pain Scale at the time of final follow-up. Patient satisfaction was assessed using a subjective questionnaire., Operative Technique: A semitendinosus tendon autograft is coursed through a transverse tunnel in the distal quadriceps tendon. The medial and lateral aspects of the graft are passed from the quadriceps tendon within subfascial tunnels to the MPFL attachment site and lateral epicondyle, respectively. The graft is fixed in 60° of knee flexion with suture anchors., Results: Surgery for recurrent instability was performed in one case. There were no cases of infection, quadriceps tendon rupture, or patella fracture. At average follow-up of 29.2months (range, 24 to 38months), outcomes were good to excellent in 4/6 of cases. Kujala scores improved significantly from 33.3 (range, three to 58) preoperatively to 70.8 (range, 39 to 96) postoperatively (p<0.05). 5/6 patients reported being satisfied to completely satisfied with their result., Conclusion: Patients undergoing bidirectional patellar stabilization with a single tendon graft showed improved postoperative functional scores. The technique is successful in reducing pain and restoring bidirectional patellar stability at 2-years follow-up., Level of Evidence: IV, retrospective case series., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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32. Triple-Row Modification of the Suture-Bridge Technique for Arthroscopic Rotator Cuff Repair.
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Ostrander RV 3rd, Smith J, and Saper M
- Abstract
Recent advances to improve outcomes in rotator cuff repair include using arthroscopic double-row suture-bridge techniques in an effort to reconstruct the rotator cuff footprint and improve fixation. However, when using this technique for larger tears, it can be difficult to get the lateral portion of the rotator cuff into an anatomic position. This report describes a triple-row modification of the suture-bridge technique that results in significantly more footprint contact area and contact pressure compared with the double-row and standard suture-bridge techniques. Maximizing the rotator cuff footprint contact area exposes more of the tendon to bone and may improve the healing potential.
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- 2016
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33. Valgus Extension Overload: Arthroscopic Decompression in the Supine-Suspended Position.
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Barousse P, Saper M, Meijer K, Roth C, and Andrews JR
- Abstract
Elbow arthroscopy is a useful tool for managing diseases of the elbow, including valgus extension overload, when conservative treatments have failed. Arthroscopic access to the elbow in the supine-suspended position is simple and reproducible with the technique described in this report. Synovial tissue can be cleared, optimizing visualization of the anatomic structures in the elbow including the posterior ulnohumeral joint. This report describes, in detail, arthroscopy of the elbow in the supine-suspended position and basic principles for arthroscopic decompression of the posterior elbow for valgus extension overload.
- Published
- 2016
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34. Arthroscopic Scapulothoracic Decompression for Snapping Scapula Syndrome.
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Saper M, Kasik C, and Dietzel D
- Abstract
Snapping scapula syndrome at the superomedial corner of the scapula can lead to significant shoulder dysfunction. Bursectomy with or without partial scapulectomy is currently the most beneficial primary method of treatment in patients in whom nonoperative therapy fails. Arthroscopic access to the scapulothoracic space is simple and reproducible with the technique described in this report. The bursal tissue can be cleared, optimizing visualization of the scapulothoracic space and the anatomic structures. Arthroscopic decompression of the scapulothoracic bursa and resection of the superomedial corner of the scapula are highlighted in a video example.
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- 2015
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35. Arthroscopic irrigation and debridement in the treatment of septic arthritis after anterior cruciate ligament reconstruction.
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Saper M, Stephenson K, and Heisey M
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- Adolescent, Adult, Anterior Cruciate Ligament surgery, Arthritis, Infectious etiology, Arthroscopy adverse effects, Female, Humans, Male, Middle Aged, Plastic Surgery Procedures adverse effects, Staphylococcal Infections therapy, Staphylococcus aureus, Transplantation, Homologous, Treatment Outcome, Young Adult, Anterior Cruciate Ligament Reconstruction adverse effects, Arthritis, Infectious therapy, Debridement methods, Therapeutic Irrigation methods
- Abstract
Purpose: To systematically review the literature and characterize the success and failure rates of arthroscopic irrigation and debridement (I & D) in the treatment of septic arthritis after anterior cruciate ligament (ACL) reconstructions. We also aimed to identify which variables affected the failure rate., Methods: Five databases (MEDLINE, Ovid, Medscape, Web of Science, and Google Scholar) were screened for clinical studies involving the treatment of septic arthritis after ACL reconstruction with arthroscopic I & D. A full-text review of eligible studies was conducted. Inclusion and exclusion criteria were applied to the searched studies. Failure of I & D was defined as the need for graft removal or revision ACL reconstructive surgery because of infection. Data from the selected studies were combined for statistical analyses to elucidate factors associated with the success or failure., Results: We identified 11 eligible studies involving 90 patients. These studies described the results of 90 arthroscopic I & D procedures with an overall success rate of 85.6%. Repeated I & D was necessary in 34.5% of patients. Removal of the graft with or without subsequent revision ACL reconstruction was reported in 13 (14.4%) cases. Statistical analysis showed that cases involving Staphylococcus aureus (P = .053), 2 or more I & D procedures (P = .029), and allografts (P < .0001) were at greater risk of failure., Conclusions: Arthroscopic I & D with graft retention is an effective treatment for patients with septic arthritis after ACL reconstruction. Factors affecting the failure rate may include graft choice and organism virulence., Level of Evidence: Level IV, systematic review of Level IV studies., (Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)
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- 2014
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36. Structure of the human class I histocompatibility antigen, HLA-A2.
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Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, and Wiley DC
- Subjects
- Animals, HLA-A2 Antigen genetics, Humans, HLA-A2 Antigen chemistry, Protein Conformation
- Published
- 2005
37. Structure of the type III secretion and substrate-binding domain of Yersinia YopH phosphatase.
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Smith CL, Khandelwal P, Keliikuli K, Zuiderweg ER, and Saper MA
- Subjects
- Amino Acid Sequence, Bacterial Outer Membrane Proteins metabolism, Binding Sites, Chromatography, Gel, Crystallography, X-Ray, Dimerization, Models, Molecular, Molecular Chaperones metabolism, Molecular Sequence Data, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Peptides metabolism, Phosphotyrosine metabolism, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Tyrosine Phosphatases metabolism, Sequence Alignment, Yersinia physiology, Bacterial Outer Membrane Proteins chemistry, Protein Tyrosine Phosphatases chemistry, Yersinia chemistry
- Abstract
Pathogenic strains of Yersinia deploy a type III secretion system to inject the potent tyrosine phosphatase YopH into host cells, where it dephosphorylates focal adhesion-associated substrates. The amino-terminal, non-catalytic domain of YopH is bifunctional; it is essential for the secretion and binding of the specific chaperone SycH, but also targets the catalytic domain to substrates in the infected cell. We describe the 2.2 A resolution crystal structure of residues 1-129 of YopH from Yersinia pseudotuberculosis. The amino-terminal alpha-helix (2-17), comprising the secretion signal, and beta-strand (24-28) of one molecule exchange with another molecule to form a domain-swapped dimer. Nuclear magnetic resonance (NMR) and gel filtration experiments demonstrated that YopH(1-129) could exist as a monomer and/or a dimer in solution. The topology of the dimer and the dynamics of a monomeric form in solution observed by NMR imply that YopH has the propensity to unfold partially. The dimer is probably not important physiologically, but may mimic how SycH binds to the exposed non-polar surfaces of a partially unfolded YopH. Phosphopeptide-induced perturbations in NMR chemical shifts define a substrate-binding surface on YopH(1-129) that includes residues previously shown by mutagenesis to be essential for YopH function.
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- 2001
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38. 1H, 15N and 13C assignments of the N-terminal domain of Yersinia outer protein H in its apo form and in complex with a phosphotyrosine peptide.
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Khandelwal P, Keliikuli K, Smit CL, Saper MA, and Zuiderweg ER
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- Macromolecular Substances, Nuclear Magnetic Resonance, Biomolecular methods, Phosphopeptides chemistry, Phosphotyrosine chemistry, Protein Binding, Protein Structure, Tertiary, Titrimetry, Apoproteins chemistry, Bacterial Outer Membrane Proteins chemistry, Bacterial Outer Membrane Proteins metabolism, Phosphopeptides metabolism, Phosphotyrosine metabolism, Protein Tyrosine Phosphatases chemistry, Protein Tyrosine Phosphatases metabolism, Yersinia chemistry
- Published
- 2001
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39. Activation of the redox-regulated molecular chaperone Hsp33--a two-step mechanism.
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Graumann J, Lilie H, Tang X, Tucker KA, Hoffmann JH, Vijayalakshmi J, Saper M, Bardwell JC, and Jakob U
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- Dimerization, Disulfides, Enzyme Activation, Heat-Shock Proteins chemistry, Heat-Shock Proteins genetics, Heat-Shock Proteins physiology, Molecular Chaperones chemistry, Molecular Chaperones genetics, Molecular Chaperones physiology, Mutagenesis, Oxidation-Reduction, Protein Processing, Post-Translational, Protein Structure, Tertiary, Temperature, Zinc metabolism, Bacterial Proteins, Heat-Shock Proteins metabolism, Molecular Chaperones metabolism
- Abstract
Background: Hsp33 is a novel redox-regulated molecular chaperone. Hsp33 is present in the reducing environment of the cytosol and is, under normal conditions, inactive. The four highly conserved cysteines found in Hsp33 constitute a novel zinc binding motif. Upon exposure to oxidative stress, Hsp33's chaperone activity is turned on. This activation process is initiated by the formation of two intramolecular disulfide bonds. Recently, the 2.2 A crystal structure of Hsp33 has been solved, revealing that Hsp33 is present as a dimer in the structure (Vijayalakshmi et al., this issue, 367-375 [1])., Results: We show here that oxidized, highly active Hsp33 is a dimer in solution. In contrast, reduced and inactive Hsp33 is monomeric. The incubation of reduced Hsp33 in H(2)O(2) leads to the simultaneous formation of two intramolecular disulfide bonds and the concomitant release of zinc. This concentration-independent step is followed by a concentration-dependent association reaction. The dimerization of Hsp33 requires highly temperature-sensitive structural rearrangements. This allows Hsp33's activation process to be greatly accelerated at heat shock temperatures., Conclusions: The regulation of Hsp33's chaperone function is highly sophisticated. On a transcriptional level, Hsp33 is under heat shock control. This increases the concentration of Hsp33 under heat and oxidative stress, a process that favors dimerization, a critical step in Hsp33's activation reaction. On a posttranslational level, Hsp33 is redox regulated. Dimerization of disulfide-bonded Hsp33 monomers leads to the formation of two extended, putative substrate binding sites. These sites might explain Hsp33's high and promiscuous affinity for unstructured protein folding intermediates.
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- 2001
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40. The 2.2 A crystal structure of Hsp33: a heat shock protein with redox-regulated chaperone activity.
- Author
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Vijayalakshmi J, Mukhergee MK, Graumann J, Jakob U, and Saper MA
- Subjects
- Amino Acid Sequence, Crystallography, X-Ray, Dimerization, Escherichia coli, Models, Molecular, Molecular Sequence Data, Oxidation-Reduction, Protein Structure, Tertiary, Zinc chemistry, Bacterial Proteins, Escherichia coli Proteins, Heat-Shock Proteins chemistry, Molecular Chaperones chemistry
- Abstract
Background: One strategy that cells employ to respond to environmental stresses (temperature, oxidation, and pathogens) is to increase the expression of heat shock proteins necessary to maintain viability. Several heat shock proteins function as molecular chaperones by binding unfolded polypeptides and preventing their irreversible aggregation. Hsp33, a highly conserved bacterial heat shock protein, is a redox-regulated molecular chaperone that appears to protect cells against the lethal effects of oxidative stress., Results: The 2.2 A crystal structure of a truncated E. coli Hsp33 (residues 1-255) reveals a domain-swapped dimer. The core domain of each monomer (1-178) folds with a central helix that is sandwiched between two beta sheets. The carboxyl-terminal region (179-235), which lacks the intact Zn binding domain of Hsp33, folds into three helices that pack on the other subunit. The interface between the two core domains is comprised of conserved residues, including a rare Glu-Glu hydrogen bond across the dyad axis. Two potential polypeptide binding sites that span the dimer are observed: a long groove containing pockets of conserved and hydrophobic residues, and an intersubunit 10-stranded beta sheet "saddle" with a largely uncharged or hydrophobic surface., Conclusions: Hsp33 is a dimer in the crystal structure. Solution studies confirmed that this dimer reflects the structural changes that occur upon activation of Hsp33 as a molecular chaperone. Patterns of conserved residues and surface charges suggest that two grooves might be potential binding sites for protein folding intermediates.
- Published
- 2001
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41. RNA methylation under heat shock control.
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Bügl H, Fauman EB, Staker BL, Zheng F, Kushner SR, Saper MA, Bardwell JC, and Jakob U
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- Amino Acid Sequence, Animals, Arabidopsis genetics, Caenorhabditis elegans genetics, Crystallography, X-Ray, Escherichia coli genetics, Humans, Methanococcus genetics, Methylation, Methyltransferases chemistry, Models, Molecular, Molecular Sequence Data, Open Reading Frames, Protein Structure, Secondary, RNA, Ribosomal, 23S metabolism, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Ribosomes metabolism, S-Adenosylmethionine metabolism, Schizosaccharomyces genetics, Sequence Alignment, Sequence Homology, Amino Acid, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Heat-Shock Proteins chemistry, Heat-Shock Proteins metabolism, Methyltransferases metabolism
- Abstract
Structural, biochemical, and genetic techniques were applied to investigate the function of FtsJ, a recently identified heat shock protein. FtsJ is well conserved, from bacteria to humans. The 1.5 A crystal structure of FtsJ in complex with its cofactor S-adenosylmethionine revealed that FtsJ has a methyltransferase fold. The molecular surface of FtsJ exposes a putative nucleic acid binding groove composed of highly conserved, positively charged residues. Substrate analysis showed that FtsJ methylates 23S rRNA within 50S ribosomal subunits in vitro and in vivo. Null mutations in ftsJ show a dramatically altered ribosome profile, a severe growth disadvantage, and a temperature-sensitive phenotype. Our results reveal an unexpected link between the heat shock response and RNA metabolism.
- Published
- 2000
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42. Structure of Hsp15 reveals a novel RNA-binding motif.
- Author
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Staker BL, Korber P, Bardwell JC, and Saper MA
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Bacterial Proteins genetics, Bacterial Proteins metabolism, Binding Sites, Conserved Sequence, Crystallography, X-Ray, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Escherichia coli chemistry, Escherichia coli genetics, Escherichia coli metabolism, Heat-Shock Proteins genetics, Heat-Shock Proteins metabolism, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Ribosomal Proteins chemistry, Ribosomal Proteins genetics, Threonine-tRNA Ligase chemistry, Threonine-tRNA Ligase genetics, Bacterial Proteins chemistry, DNA-Binding Proteins chemistry, Escherichia coli Proteins, Heat-Shock Proteins chemistry, RNA-Binding Proteins chemistry
- Abstract
We have solved the crystal structure of the heat shock protein Hsp15, a newly isolated and very highly inducible heat shock protein that binds the ribosome. Comparison of its structure with those of two RNA-binding proteins, ribosomal protein S4 and threonyl-tRNA synthetase, reveals a novel RNA-binding motif. This newly recognized motif is remarkably common, present in at least eight different protein families that bind RNA. The motif's surface is populated by conserved, charged residues that define a likely RNA-binding site. An intriguing pattern emerges: stress proteins, ribosomal proteins and tRNA synthetases repeatedly share a conserved motif. This may imply a hitherto unrecognized functional similarity between these three protein classes.
- Published
- 2000
- Full Text
- View/download PDF
43. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A.
- Author
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Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, and Saper MA
- Subjects
- Amino Acid Sequence, Binding Sites, Crystallography, X-Ray, Disulfides chemistry, Humans, Molecular Sequence Data, Protein Conformation, Sequence Alignment, Substrate Specificity, Models, Molecular, Protein Tyrosine Phosphatases chemistry, cdc25 Phosphatases
- Abstract
Cdc25 phosphatases activate the cell division kinases throughout the cell cycle. The 2.3 A structure of the human Cdc25A catalytic domain reveals a small alpha/beta domain with a fold unlike previously described phosphatase structures but identical to rhodanese, a sulfur-transfer protein. Only the active-site loop, containing the Cys-(X)5-Arg motif, shows similarity to the tyrosine phosphatases. In some crystals, the catalytic Cys-430 forms a disulfide bond with the invariant Cys-384, suggesting that Cdc25 may be self-inhibited during oxidative stress. Asp-383, previously proposed to be the general acid, instead serves a structural role, forming a conserved buried salt-bridge. We propose that Glu-431 may act as a general acid. Structure-based alignments suggest that the noncatalytic domain of the MAP kinase phosphatases will share this topology, as will ACR2, a eukaryotic arsenical resistance protein.
- Published
- 1998
- Full Text
- View/download PDF
44. Structure of benzyl T-antigen disaccharide bound to Amaranthus caudatus agglutinin.
- Author
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Transue TR, Smith AK, Mo H, Goldstein IJ, and Saper MA
- Subjects
- Benzyl Compounds, Crystallography, X-Ray methods, Dimerization, Edible Grain, Models, Molecular, Plant Lectins, Ribosome Inactivating Proteins, Ribosome Inactivating Proteins, Type 1, Seeds, Antigens, Viral, Tumor chemistry, Disaccharides, Lectins chemistry, Protein Conformation
- Abstract
Amaranthus caudatus agglutinin contains a novel arrangement of four beta-trefoil domains. The sugar-binding site provides specificity for the carcinoma-associated T-antigen disaccharide even when 'masked' by other sugars.
- Published
- 1997
- Full Text
- View/download PDF
45. Structure and function of the protein tyrosine phosphatases.
- Author
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Fauman EB and Saper MA
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, Cell Cycle Proteins chemistry, Cell Cycle Proteins metabolism, Cell Cycle Proteins physiology, Conserved Sequence, Cyanobacteria enzymology, Cyclin-Dependent Kinase Inhibitor Proteins, Dual-Specificity Phosphatases, Humans, Hydrolysis, Models, Molecular, Molecular Sequence Data, Molecular Weight, Phosphoprotein Phosphatases metabolism, Phosphorylation, Phosphotyrosine metabolism, Protein Conformation, Protein Tyrosine Phosphatases, Non-Receptor, Rhodobacter enzymology, Salmonella enzymology, Substrate Specificity, Tyrosine metabolism, cdc25 Phosphatases, Protein Tyrosine Phosphatases chemistry, Protein Tyrosine Phosphatases metabolism, Saccharomyces cerevisiae Proteins
- Abstract
The tyrosine and dual-specificity phosphatases are involved in signaling, cell growth and differentiation, and the cell cycle. The enzymes share a common catalytic mechanism mediated by an active site cysteine, arginine and aspartic acid. Supplementary domains assist in targeting and substrate specificity.
- Published
- 1996
- Full Text
- View/download PDF
46. Form and function in protein dephosphorylation.
- Author
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Denu JM, Stuckey JA, Saper MA, and Dixon JE
- Subjects
- Animals, Binding Sites, Catalysis, Hydrogen Bonding, Mice, Phosphorylation, Protein Tyrosine Phosphatases chemistry, Signal Transduction physiology, Structure-Activity Relationship, Models, Molecular, Protein Conformation, Protein Processing, Post-Translational, Protein Tyrosine Phosphatases physiology
- Published
- 1996
- Full Text
- View/download PDF
47. Crystal structure of the dual specificity protein phosphatase VHR.
- Author
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Yuvaniyama J, Denu JM, Dixon JE, and Saper MA
- Subjects
- Amino Acid Sequence, Binding Sites, Crystallography, X-Ray, Dual Specificity Phosphatase 3, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Phosphorylation, Phosphoserine metabolism, Phosphothreonine metabolism, Phosphotyrosine metabolism, Protein Folding, Protein Tyrosine Phosphatases metabolism, Sequence Alignment, Substrate Specificity, Water metabolism, Yersinia enzymology, Protein Conformation, Protein Structure, Secondary, Protein Tyrosine Phosphatases chemistry
- Abstract
Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Here, the crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), was determined at 2.1 angstrom resolution. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A "recognition region," connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs.
- Published
- 1996
- Full Text
- View/download PDF
48. A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase.
- Author
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Schubert HL, Fauman EB, Stuckey JA, Dixon JE, and Saper MA
- Subjects
- Amino Acid Sequence, Aspartic Acid chemistry, Binding Sites, Crystallization, Crystallography, X-Ray, Cysteine chemistry, Models, Molecular, Molecular Sequence Data, Mutation, Protein Tyrosine Phosphatases metabolism, Serine chemistry, Sulfates chemistry, Sulfates metabolism, Tungsten Compounds metabolism, Water chemistry, Protein Conformation, Protein Tyrosine Phosphatases chemistry, Yersinia enzymology
- Abstract
Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular signal transduction pathways that regulate cell transformation, growth, and proliferation. The structures of several different PTPases have revealed a conserved active site architecture in which a phosphate-binding loop, together with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate and poise it for nucleophilic attack by an invariant cysteine nucleophile. We previously reported that binding of tungstate to the Yop51 PTPase from Yersinia induced a loop conformational change that moved aspartic acid 356 into the active site, where it can function as a general acid. This is consistent with the aspartic acid donating a proton to the tyrosyl leaving group during the initial hydrolysis step. In this report, using a similar structure of the inactive Cys 403-->Ser mutant of the Yersinia PTPase complexed with sulfate, we detail the structural and functional details of this conformational change. In response to oxyanion binding, small perturbations occur in active site residues, especially Arg 409, and trigger the loop to close. Interestingly, the peptide bond following Asp 356 has flipped to ligate a buried, active site water molecule that also hydrogen bonds to the bound sulfate anion and two invariant glutamines. Loop closure also significantly decreases the solvent accessibility of the bound oxyanion and could effectively shield catalytic intermediates from phosphate acceptors other than water. We speculate that the intrinsic loop flexibility of different PTPases may be related to their catalytic rate and may play a role in the wide range of activities observed within this enzyme family.
- Published
- 1995
- Full Text
- View/download PDF
49. The Cys(X)5Arg catalytic motif in phosphoester hydrolysis.
- Author
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Zhang ZY, Wang Y, Wu L, Fauman EB, Stuckey JA, Schubert HL, Saper MA, and Dixon JE
- Subjects
- Amino Acid Sequence, Base Sequence, Binding Sites, Kinetics, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides chemistry, Protein Structure, Tertiary, Sequence Alignment, Sequence Homology, Amino Acid, Spectrophotometry, Ultraviolet, Structure-Activity Relationship, Yersinia enzymology, Protein Tyrosine Phosphatases chemistry
- Abstract
The Yersinia protein tyrosine phosphatase (PTPase) was identified in the genus of bacteria responsible for the plague or the Black Death and was shown to be essential for pathogenesis. The three-dimensional structure of the catalytic domain of the Yersinia PTPase has been solved, and this information along with a detailed kinetic analysis has led to a better understanding of the catalytic mechanism of the PTPase. Mutational and chemical modification experiments have established that an invariant Cys residue (Cys403) is directly involved in formation of a covalent phosphoenzyme intermediate. We have shown that Arg409 plays a critical role in PTPase action and that the Cys(X)5Arg active site motif forms a phosphate-binding loop which appears to represent the essential features necessary for catalysis by the PTPases, the dual specific phosphatases, and the low molecular weight acid phosphatases.
- Published
- 1994
- Full Text
- View/download PDF
50. Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate.
- Author
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Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, and Saper MA
- Subjects
- Amino Acid Sequence, Crystallography, Cysteine, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Structure, Secondary, Tungsten Compounds chemistry, Bacterial Outer Membrane Proteins chemistry, Protein Tyrosine Phosphatases chemistry, Yersinia enterocolitica enzymology
- Abstract
Protein tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation. Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase, Yop51, that enters and suppresses host immune cells. Though the catalytic domain is only approximately 20% identical to human PTP1B, the Yersinia PTPase contains all of the invariant residues present in eukaryotic PTPases, including the nucleophilic Cys 403 which forms a phosphocysteine intermediate during catalysis. We present here structures of the unliganded (2.5 A resolution) and tungstate-bound (2.6 A) crystal forms which reveal that Cys 403 is positioned at the centre of a distinctive phosphate-binding loop. This loop is at the hub of several hydrogen-bond arrays that not only stabilize a bound oxyanion, but may activate Cys 403 as a reactive thiolate. Binding of tungstate triggers a conformational change that traps the oxyanion and swings Asp 356, an important catalytic residue, by approximately 6 A into the active site. The same anion-binding loop in PTPases is also found in the enzyme rhodanese.
- Published
- 1994
- Full Text
- View/download PDF
Catalog
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