21 results on '"Palmer DR"'
Search Results
2. Conclusions
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
3. The United Kingdom
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
4. Introduction
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
5. The United States of America
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
6. Australia
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
7. Does depression moderate the relationship between pain and suicidality in adolescence? A moderated network analysis
- Author
-
Hinze, Verena, primary, Ford, Tamsin, additional, Crane, Catherine, additional, Haslbeck, Jonas M.B., additional, Hawton, Keith, additional, Gjelsvik, Bergljot, additional, Allwood, Matthew, additional, Aukland, Louise, additional, Casey, Triona, additional, De Wilde, Katherine, additional, Farley, Eleanor-Rose, additional, Fletcher, Katie, additional, Kappelmann, Nils, additional, Kuyken, Prof. Willem, additional, Laws, Suzannah, additional, Lord, Liz, additional, Medlicott, Emma, additional, Montero-Marin, Dr. Jesus, additional, Nuthall, Elizabeth, additional, Palmer, Dr. Lucy, additional, Petit, Ariane, additional, Philips, Alice, additional, Pryor-Nitsch, Isobel, additional, Radley, Lucy, additional, Raja, Anam, additional, Shackleford, Jeremy, additional, Sonley, Anna, additional, Taylor, Dr. Laura, additional, Warriner, Lucy, additional, Williams, Prof. J.Mark G., additional, Bennett, Marc, additional, Dalgleish, Prof. Tim, additional, Dunning, Darren, additional, Griffiths, Kirsty, additional, Knight, Rachel, additional, Vainre, Maris, additional, Ahmed, Saz, additional, Blakemore, Prof. Sarah-Jayne, additional, Pi-Sunyer, Blanca Piera, additional, Foulkes, Lucy, additional, Leung, Jovita, additional, Sakhardande, Ashok, additional, Ukoumunne, Dr. Obioha C, additional, Ball, Susan, additional, Byford, Prof. Sarah, additional, Ganguli, Poushali, additional, Greenberg, Prof. Mark T., additional, Viner, Prof Russell M., additional, and Wainman, Brian, additional
- Published
- 2021
- Full Text
- View/download PDF
8. Technology-enhanced laboratory (TEL) sessions for Masters of Pharmacy (MPharm) students to promote active learning: identification and management of dysrhythmias
- Author
-
Dr Rajendran Gopalan, Professor Timothy Martin Palmer, Dr Bishwa Tuladhar, Mr Darren Brown, Dr Diana Wood.
- Published
- 2016
9. Countering Economic Crime
- Author
-
Palmer, Dr Axel, primary
- Published
- 2017
- Full Text
- View/download PDF
10. Target-specific requirements for RNA interference can arise through restricted RNA amplification despite the lack of specialized pathways.
- Author
-
Knudsen-Palmer DR, Raman P, Ettefa F, De Ravin L, and Jose AM
- Subjects
- Animals, RNA-Binding Proteins, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Caenorhabditis elegans Proteins genetics, RNA Interference, RNA, Double-Stranded metabolism, RNA, Double-Stranded genetics
- Abstract
Since double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematode Caenorhabditis elegans can selectively impair the silencing of some genes. Here, we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changing cis -regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells, and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, are enriched within 'pUG zones' matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs., Competing Interests: DK, PR, FE, LD, AJ No competing interests declared, (© 2024, Knudsen-Palmer et al.)
- Published
- 2024
- Full Text
- View/download PDF
11. The chondrocyte "mechanome": Activation of the mechanosensitive ion channels TRPV4 and PIEZO1 drives unique transcriptional signatures.
- Author
-
Nims R, Palmer DR, Kassab J, Zhang B, and Guilak F
- Subjects
- Animals, Chondrogenesis, Mechanotransduction, Cellular, Swine, Chondrocytes metabolism, Ion Channels metabolism, Ion Channels genetics, Transcriptome, TRPV Cation Channels metabolism, TRPV Cation Channels genetics
- Abstract
The mechanosensitive ion channels Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 transduce physiologic and supraphysiologic magnitudes of mechanical signals in the chondrocyte, respectively. TRPV4 activation promotes chondrogenesis, while PIEZO1 activation by supraphysiologic deformations drives cell death. The mechanisms by which activation of these channels discretely drives changes in gene expression to alter cell behavior remain to be determined. To date, no studies have contrasted the transcriptomic response to activation of these channels nor has any published data attempted to correlate these transcriptomes to alterations in cellular function. This study used RNA sequencing to comprehensively investigate the transcriptomes associated with activation of TRPV4 or PIEZO1, revealing that TRPV4 and PIEZO drive distinct transcriptomes and also exhibit unique co-regulated clusters of genes. Notably, activation of PIEZO1 through supraphysiologic deformation induced a transient inflammatory profile that overlapped with the interleukin (IL)-1-responsive transcriptome and contained genes associated with cartilage degradation and osteoarthritis progression. However, both TRPV4 and PIEZO1 were also shown to elicit anabolic effects. PIEZO1 expression promoted a pro-chondrogenic transcriptome under unloaded conditions, and daily treatment with PIEZO1 agonist Yoda1 significantly increased sulfated glycosaminoglycan deposition in vitro. These findings emphasize the presence of a broad "mechanome" with distinct effects of TRPV4 and PIEZO1 activation in chondrocytes, suggesting complex roles for PIEZO1 in both the physiologic and pathologic responses of chondrocytes. The identification of transcriptomic profiles unique to or shared by PIEZO1 and TRPV4 (distinct from IL-1-induced inflammation) could inform future therapeutic designs targeting these channels for the management and treatment of osteoarthritis., (© 2024 Federation of American Societies for Experimental Biology.)
- Published
- 2024
- Full Text
- View/download PDF
12. Treatment with PB125 ® Increases Femoral Long Bone Strength in 15-Month-Old Female Hartley Guinea Pigs.
- Author
-
Andrie KM, Palmer DR, Wahl O, Bork S, Campbell M, Walsh MA, Sanford J, Musci RV, Hamilton KL, Santangelo KS, and Puttlitz CM
- Subjects
- Animals, Female, Guinea Pigs, Male, Bone and Bones, X-Ray Microtomography, Disease Models, Animal, NF-E2-Related Factor 2 pharmacology, NF-E2-Related Factor 2 therapeutic use, Osteoarthritis prevention & control
- Abstract
Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a transcription factor that serves as a master regulator of anti-inflammatory agents, phase I xenobiotic, and phase II antioxidant enzymes, all of which provide a cytoprotective role during disease progression. We hypothesized that oral administration of a purported phytochemical Nrf2-activator, PB125
® , would increase long bone strength in aging Hartley guinea pigs, a model prone to musculoskeletal decline. Male (N = 56) and female (N = 56) guinea pigs were randomly assigned to receive daily oral treatment with either PB125® or vehicle control. Animals were treated for a consecutive 3-months (starting at 2-months of age) or 10-months (starting at 5-months of age) and sacrificed at 5-months or 15-months of age, respectively. Outcome measures included: (1) ANY-maze™ enclosure monitoring, (2) quantitative microcomputed tomography, and (3) biomechanical testing. Treatment with PB125® for 10 months resulted in increased long bone strength as determined by ultimate bending stress in female Hartley guinea pigs. In control groups, increasing age resulted in significant effects on geometric and structural properties of long bones, as well as a trending increase in ultimate bending stress. Furthermore, both age and sex had a significant effect on the geometric properties of both cortical and trabecular bone. Collectively, this work suggests that this nutraceutical may serve as a promising target and preventive measure in managing the decline in bone mass and quality documented in aging patients. Auxiliary to this main goal, this work also capitalized upon 5 and 15-month-old male and female animals in the control group to characterize age- and sex-specific differences on long bone geometric, structural, and material properties in this animal model., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)- Published
- 2024
- Full Text
- View/download PDF
13. Modeling Preweaning Dairy Calf Performance.
- Author
-
Larson R
- Subjects
- Animals, Body Weight, Cattle, Diet veterinary, Nutritional Status, Weaning, Animal Feed analysis, Milk metabolism
- Abstract
The development of modeling concepts with the 2001 NRC (National Research Council Nutrient Requirements of Dairy Cattle represented a big step toward understanding and applying the underlying mechanisms associated with young calf growth. Factors such as the plane of nutrition being provided (protein and energy), breed and environmental stressors impact calf growth. Investigation into delivering the proper amounts of energy and protein through the liquid and dry feeds to optimize growth needs to continue as well as further defining the most effective means to transition from the nonruminant to ruminant phase while minimizing postweaning lag., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
14. Validity and Reliability of the Updated CDC Worksite Health ScoreCard.
- Author
-
Roemer EC, Kent KB, Mummert A, McCleary K, Palmer JB, Lang JE, Matson Koffman DM, and Goetzel RZ
- Subjects
- Female, Humans, Interviews as Topic, Male, Pilot Projects, Qualitative Research, Reproducibility of Results, United States, Centers for Disease Control and Prevention, U.S., Health Status, Health Surveys standards, Workplace statistics & numerical data
- Abstract
Objective: The aim of this study was to evaluate the reliability and validity of the updated 2019 CDC Worksite Health ScoreCard (CDC ScoreCard), which includes four new modules., Methods: We pilot tested the updated instrument at 93 worksites, examining question response concurrence between two representatives from each worksite. We conducted cognitive interviews and site visits to evaluate face validity, and refined the instrument for public distribution., Results: The mean question concurrence rate was 73.4%. Respondents reported the tool to be useful for assessing current workplace programs and planning future initiatives. On average, 43% of possible interventions included in the CDC ScoreCard were in place at the pilot sites., Conclusion: The updated CDC ScoreCard is a valid and reliable tool for assessing worksite health promotion policies, educational and lifestyle counseling programs, environmental supports, and health benefits.
- Published
- 2019
- Full Text
- View/download PDF
15. The Associations of Multimorbidity With Health-Related Productivity Loss in a Large and Diverse Public Sector Setting: A Cross-Sectional Survey.
- Author
-
Wang L, Cocker F, Kilpatrick M, Otahal P, Si L, Palmer AJ, and Sanderson K
- Subjects
- Adult, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Self Report, State Government, Tasmania epidemiology, Absenteeism, Chronic Disease epidemiology, Comorbidity, Efficiency, Presenteeism, Public Sector statistics & numerical data
- Abstract
Objective: To evaluate absenteeism, presenteeism, and total lost productive time (LPT) associated with multimorbidity., Methods: Cross-sectional data from 3228 state-government employees from Tasmania were collected in 2013. The validated measures of absenteeism, presenteeism, and LPT were obtained from employees' self-reported data over a 28-day period. Analyses were stratified by sex. Negative binomial models were used to estimate the associations between multimorbidity and LPT., Results: The average health-related total LPT was 1.2 (standard deviation [SD] = 2.4) and 1.7 (SD = 3.5) days for men and women with multimorbidity, respectively. Women (rate ratio [RR] = 2.9, 95% confidence interval [CI] 1.8 to 4.9) and men (RR = 4.4, 95%CI 3.0 to 6.2) with 4+ chronic conditions were significantly more likely to report LPT compared with those without any chronic conditions., Conclusion: We found multimorbidity is of concern within the workforce, with a positive association of multimorbidity and LPT observed, and significant differences in LPT between men and women reporting multimorbidity.
- Published
- 2018
- Full Text
- View/download PDF
16. Simultaneous Measurement of Glucose-6-phosphate 3-Dehydrogenase (NtdC) Catalysis and the Nonenzymatic Reaction of Its Product: Kinetics and Isotope Effects on the First Step in Kanosamine Biosynthesis.
- Author
-
Vetter ND and Palmer DR
- Subjects
- Bacillus subtilis genetics, Bacterial Proteins genetics, Biocatalysis, Deuterium, Escherichia coli genetics, Escherichia coli metabolism, Glucosamine biosynthesis, Glucose-6-Phosphate, Glucosephosphate Dehydrogenase genetics, Glutamic Acid metabolism, Hydrogen-Ion Concentration, Kinetics, NAD metabolism, Operon, Oxidation-Reduction, Recombinant Proteins genetics, Recombinant Proteins metabolism, Thermodynamics, Bacillus subtilis metabolism, Bacterial Proteins metabolism, Gene Expression Regulation, Bacterial, Glucosephosphate Dehydrogenase metabolism, Protons
- Abstract
Glucose-6-phosphate 3-dehydrogenase (NtdC) is an NAD-dependent oxidoreductase encoded in the NTD operon of Bacillus subtilis. The oxidation of glucose 6-phosphate by NtdC is the first step in kanosamine biosynthesis. The product, 3-oxo-d-glucose 6-phosphate (3oG6P), has never been synthesized or isolated. The NtdC-catalyzed reaction is very slow at low and neutral pH, and its rate increases to a maximum near pH 9.5. However, under alkaline conditions, the product is not stable because of ring opening followed by deprotonation of the 1,3-dicarbonyl compound. The absorbance band due to this enolate at 310 nm overlaps with that of the other enzymatic product, NADH, complicating kinetic measurements. We report the deconvolution of the resulting spectra of the reaction to determine the rate constants and likely kinetic mechanism. In doing so, we were able to determine the extinction coefficient of the enolate of 3oG6P (23000 M
-1 cm-1 ), which allowed the measurement of the first-order rate constant (5.51 × 10-3 s-1 ) and activation energy (93 kJ mol-1 ) of nonenzymatic enolate formation. Using deuterium-labeled substrates, we show that hydride transfer from carbon 3 is partially rate-limiting in the enzymatic reaction, and deuterium substitution on carbon 2 has no significant effect on the enzymatic reaction but lowers the rate of deprotonation of 3oG6P 4-fold. These experiments clearly establish the regiochemistry of the reactions. Coupling of the NtdC reaction with the subsequent step in the pathway, NtdA-catalyzed glutamate-dependent amino transfer, has a small but significant effect on the rate of NAD reduction, consistent with these enzymes working together to process the unstable metabolite.- Published
- 2017
- Full Text
- View/download PDF
17. Evidence of Allosteric Enzyme Regulation via Changes in Conformational Dynamics: A Hydrogen/Deuterium Exchange Investigation of Dihydrodipicolinate Synthase.
- Author
-
Sowole MA, Simpson S, Skovpen YV, Palmer DR, and Konermann L
- Subjects
- Allosteric Regulation, Crystallography, X-Ray, Deuterium chemistry, Hydrogen chemistry, Protein Conformation, Hydro-Lyases chemistry
- Abstract
Dihydrodipicolinate synthase is a tetrameric enzyme of the diaminopimelate pathway in bacteria and plants. The protein catalyzes the condensation of pyruvate (Pyr) and aspartate semialdehyde en route to the end product lysine (Lys). Dihydrodipicolinate synthase from Campylobacter jejuni (CjDHDPS) is allosterically inhibited by Lys. CjDHDPS is a promising antibiotic target, as highlighted by the recent development of a potent bis-lysine (bisLys) inhibitor. The mechanism whereby Lys and bisLys allosterically inhibit CjDHDPS remains poorly understood. In contrast to the case for other allosteric enzymes, crystallographically detectable conformational changes in CjDHDPS upon inhibitor binding are very minor. Also, it is difficult to envision how Pyr can access the active site; the available X-ray data seemingly imply that each turnover step requires diffusion-based mass transfer through a narrow access channel. This study employs hydrogen/deuterium exchange mass spectrometry for probing the structure and dynamics of CjDHDPS in a native solution environment. The deuteration kinetics reveal that the most dynamic protein regions are in the direct vicinity of the substrate access channel. This finding is consistent with the view that transient opening/closing fluctuations facilitate access of the substrate to the active site. Under saturating conditions, both Lys and bisLys cause dramatically reduced dynamics in the inhibitor binding region. In addition, rigidification extends to regions close to the substrate access channel. This finding strongly suggests that allosteric inhibitors interfere with conformational fluctuations that are required for CjDHDPS substrate turnover. In particular, our data imply that Lys and bisLys suppress opening/closing events of the access channel, thereby impeding diffusion of the substrate into the active site. Overall, this work illustrates why allosteric control does not have to be associated with crystallographically detectable large-scale transitions. Our experiments provide evidence that in CjDHDPS allostery is mediated by changes in the extent of thermally activated conformational fluctuations.
- Published
- 2016
- Full Text
- View/download PDF
18. Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from Campylobacter jejuni.
- Author
-
Skovpen YV, Conly CJ, Sanders DA, and Palmer DR
- Subjects
- Allosteric Regulation, Crystallography, X-Ray, Enzyme Inhibitors chemistry, Biomimetics, Campylobacter jejuni enzymology, Enzyme Inhibitors pharmacology, Hydro-Lyases antagonists & inhibitors
- Abstract
Dihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and β-aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein-inhibitor complex at 2.2 Å resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the α-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a Ki near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 Å. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development.
- Published
- 2016
- Full Text
- View/download PDF
19. Identification of Interactions between Abscisic Acid and Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase.
- Author
-
Galka MM, Rajagopalan N, Buhrow LM, Nelson KM, Switala J, Cutler AJ, Palmer DR, Loewen PC, Abrams SR, and Loewen MC
- Subjects
- Abscisic Acid chemistry, Amino Acid Sequence, Arabidopsis metabolism, Binding Sites, Molecular Sequence Data, Protein Binding, Ribulose-Bisphosphate Carboxylase metabolism, Abscisic Acid metabolism, Ribulose-Bisphosphate Carboxylase chemistry
- Abstract
Abscisic acid ((+)-ABA) is a phytohormone involved in the modulation of developmental processes and stress responses in plants. A chemical proteomics approach using an ABA mimetic probe was combined with in vitro assays, isothermal titration calorimetry (ITC), x-ray crystallography and in silico modelling to identify putative (+)-ABA binding-proteins in crude extracts of Arabidopsis thaliana. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) was identified as a putative ABA-binding protein. Radiolabelled-binding assays yielded a Kd of 47 nM for (+)-ABA binding to spinach Rubisco, which was validated by ITC, and found to be similar to reported and experimentally derived values for the native ribulose-1,5-bisphosphate (RuBP) substrate. Functionally, (+)-ABA caused only weak inhibition of Rubisco catalytic activity (Ki of 2.1 mM), but more potent inhibition of Rubisco activation (Ki of ~ 130 μM). Comparative structural analysis of Rubisco in the presence of (+)-ABA with RuBP in the active site revealed only a putative low occupancy (+)-ABA binding site on the surface of the large subunit at a location distal from the active site. However, subtle distortions in electron density in the binding pocket and in silico docking support the possibility of a higher affinity (+)-ABA binding site in the RuBP binding pocket. Overall we conclude that (+)-ABA interacts with Rubisco. While the low occupancy (+)-ABA binding site and weak non-competitive inhibition of catalysis may not be relevant, the high affinity site may allow ABA to act as a negative effector of Rubisco activation.
- Published
- 2015
- Full Text
- View/download PDF
20. Kinetic evaluation of glucose 1-phosphate analogues with a thymidylyltransferase using a continuous coupled enzyme assay.
- Author
-
Forget SM, Jee A, Smithen DA, Jagdhane R, Anjum S, Beaton SA, Palmer DR, Syvitski RT, and Jakeman DL
- Subjects
- Anti-Bacterial Agents chemical synthesis, Bacterial Proteins antagonists & inhibitors, Diphosphates analysis, Enzyme Assays, Enzyme Inhibitors chemical synthesis, Kinetics, Nucleotidyltransferases antagonists & inhibitors, Recombinant Proteins chemistry, Spectrophotometry, Streptococcus pneumoniae chemistry, Streptococcus pneumoniae enzymology, Anti-Bacterial Agents chemistry, Bacterial Proteins chemistry, Enzyme Inhibitors chemistry, Glucosephosphates chemistry, Nucleotidyltransferases chemistry
- Abstract
Cps2L, a thymidylytransferase, is the first enzyme in Streptococcus pneumoniae L-rhamnose biosynthesis and an antibacterial target. We herein report the evaluation of six sugar phosphate analogues selected to further probe Cps2L substrate tolerance. A modified continuous spectrophotometric assay was employed for facile detection of pyrophosphate (PPi) released from nucleotidylyltransfase-catalysed condensation of sugar 1-phosphates and nucleoside triphosphates to produce sugar nucleotides. Additionally, experiments using waterLOGSY NMR spectroscopy were investigated as a complimentary method to evaluate binding affinity to Cps2L.
- Published
- 2015
- Full Text
- View/download PDF
21. Tyrosine 110 plays a critical role in regulating the allosteric inhibition of Campylobacter jejuni dihydrodipicolinate synthase by lysine.
- Author
-
Conly CJ, Skovpen YV, Li S, Palmer DR, and Sanders DA
- Subjects
- Allosteric Regulation drug effects, Catalytic Domain drug effects, Enzyme Inhibitors metabolism, Hydro-Lyases antagonists & inhibitors, Hydro-Lyases genetics, Ligands, Lysine metabolism, Models, Molecular, Movement, Mutagenesis, Site-Directed, Mutation, Campylobacter jejuni enzymology, Enzyme Inhibitors pharmacology, Hydro-Lyases chemistry, Hydro-Lyases metabolism, Lysine pharmacology, Tyrosine metabolism
- Abstract
Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-β-semialdehyde, forming an unstable product that is dehydrated to dihydrodipicolinate. The tetrameric enzyme is allosterically inhibited by l-lysine, and a better understanding of the allosteric inhibition mechanism is necessary for the design of potent antibacterial therapeutics. Here we describe the high-resolution crystal structures of DHDPS from Campylobacter jejuni with and without its inhibitor bound to the allosteric sites. These structures reveal a role for Y110 in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to phenylalanine results in insensitivity to lysine inhibition, although the mutant crystal structure reveals that lysine does bind in the allosteric site. Comparison of the lysine-bound Y110F structure with wild-type structures reveals that key structural changes due to lysine binding are absent in this mutant.
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.