24 results on '"Abola EE"'
Search Results
2. Serial Crystallography for Structure-Based Drug Discovery.
- Author
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Zhu L, Chen X, Abola EE, Jing L, and Liu W
- Subjects
- Crystallography, X-Ray instrumentation, Drug Discovery instrumentation, Humans, Lasers, Protein Conformation, Receptors, G-Protein-Coupled metabolism, Structure-Activity Relationship, Synchrotrons, Crystallography, X-Ray methods, Drug Discovery methods, Receptors, G-Protein-Coupled chemistry
- Abstract
Rational drug discovery has greatly accelerated the development of safer and more efficacious therapeutics, assisted significantly by insights from experimentally determined 3D structures of ligands in complex with their targets. Serial crystallography (SX) with X-ray free-electron lasers has enabled structural determination using micrometer- or nanometer-size crystals. This technology, applied in the past decade to solve structures of notoriously difficult-to-study drug targets at room temperature, has now been adapted for use in synchrotron radiation facilities. Ultrashort time scales allow time-resolved characterization of dynamic structural changes and pave the road to study the molecular mechanisms by 'molecular movie.' This article summarizes the latest progress in SX technology and deliberates its demanding applications in future structure-based drug discovery., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
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3. Crystallization of Membrane Proteins: An Overview.
- Author
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Ishchenko A, Abola EE, and Cherezov V
- Subjects
- Animals, Bacteria chemistry, Crystallography, X-Ray instrumentation, Databases, Factual, Detergents chemistry, Gene Expression, Insecta chemistry, Lipids chemistry, Mammals metabolism, Membrane Proteins biosynthesis, Membrane Proteins genetics, Membrane Proteins isolation & purification, Models, Molecular, Propylamines chemistry, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins ultrastructure, Crystallization methods, Crystallography, X-Ray methods, Membrane Proteins ultrastructure
- Abstract
Membrane proteins are crucial components of cellular membranes and are responsible for a variety of physiological functions. The advent of new tools and technologies for structural biology of membrane proteins has led to a significant increase in the number of structures deposited to the Protein Data Bank during the past decade. This new knowledge has expanded our fundamental understanding of their mechanism of function and contributed to the drug-design efforts. In this chapter we discuss current approaches for membrane protein expression, solubilization, crystallization, and data collection. Additionally, we describe the protein quality-control assays that are often instrumental as a guideline for a shorter path toward the structure.
- Published
- 2017
- Full Text
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4. Fluorescence Recovery After Photobleaching in Lipidic Cubic Phase (LCP-FRAP): A Precrystallization Assay for Membrane Proteins.
- Author
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Fenalti G, Abola EE, Wang C, Wu B, and Cherezov V
- Subjects
- Animals, Humans, Crystallization methods, Fluorescence Recovery After Photobleaching methods, Lipids chemistry, Receptors, G-Protein-Coupled chemistry
- Abstract
Crystallization of integral membrane proteins (MPs) is notoriously difficult, given their poor stability outside native membrane environment and due to the interference of detergent micelles with crystallization process. MP crystallization in a membrane mimetic matrix, known as lipidic cubic phase (LCP), has recently started to gain popularity, following successes in structure determination of G protein-coupled receptors (GPCRs), transporters, and enzymes. Unlike crystallization trials in aqueous solutions where protein molecules are free to move, diffusion of MPs in LCP is restricted, and, thus, a high level of protein mobility can serve as an early indication for subsequent crystallization success. Prompted by our initial observations that precipitant conditions can dramatically affect diffusion of GPCRs in LCP, we have developed a simple precrystallization assay, based on measuring protein diffusion at a number of different conditions by fluorescence recovery after photobleaching (LCP-FRAP). Over the last few years, the LCP-FRAP assay was incorporated in our GPCR structure determination pipeline and proved as a powerful technique allowing for a faster identification of crystallization conditions for many different receptors. The assay is used to screen for the best protein constructs, ligands, LCP host lipids, precipitants, and additives, thereby focusing subsequent crystallization trials on the most promising parts of the multidimensional crystallization phase diagram, substantially increasing the likelihood of finding the right crystallization condition. Here, we describe our LCP-FRAP protocols for guiding GPCR crystallization, which can be adapted to any other MP, and discuss some of the critical considerations related to application of this assay., (© 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
5. Allosteric sodium in class A GPCR signaling.
- Author
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Katritch V, Fenalti G, Abola EE, Roth BL, Cherezov V, and Stevens RC
- Subjects
- Allosteric Regulation, Animals, Humans, Signal Transduction, Receptors, G-Protein-Coupled metabolism, Sodium metabolism
- Abstract
Despite their functional and structural diversity, G-protein-coupled receptors (GPCRs) share a common mechanism of signal transduction via conformational changes in the seven-transmembrane (7TM) helical domain. New major insights into this mechanism come from the recent crystallographic discoveries of a partially hydrated sodium ion that is specifically bound in the middle of the 7TM bundle of multiple class A GPCRs. This review discusses the remarkable structural conservation and distinct features of the Na(+) pocket in this most populous GPCR class, as well as the conformational collapse of the pocket upon receptor activation. New insights help to explain allosteric effects of sodium on GPCR agonist binding and activation, and sodium's role as a potential co-factor in class A GPCR function., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
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6. Structural and biochemical characterization of the therapeutic Anabaena variabilis phenylalanine ammonia lyase.
- Author
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Wang L, Gamez A, Archer H, Abola EE, Sarkissian CN, Fitzpatrick P, Wendt D, Zhang Y, Vellard M, Bliesath J, Bell SM, Lemontt JF, Scriver CR, and Stevens RC
- Subjects
- Animals, Bacterial Proteins genetics, Bacterial Proteins metabolism, Binding Sites, Crystallography, X-Ray, Enzyme Stability, Gene Duplication, Hydrogen-Ion Concentration, Ligands, Mice, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases metabolism, Phenylalanine Ammonia-Lyase genetics, Phenylalanine Ammonia-Lyase metabolism, Point Mutation, Protein Engineering, Protein Structure, Quaternary, Temperature, Anabaena variabilis enzymology, Bacterial Proteins chemistry, Phenylalanine Ammonia-Lyase chemistry, Protein Structure, Tertiary
- Abstract
We have recently observed promising success in a mouse model for treating the metabolic disorder phenylketonuria with phenylalanine ammonia lyase (PAL) from Rhodosporidium toruloides and Anabaena variabilis. Both molecules, however, required further optimization in order to overcome problems with protease susceptibility, thermal stability, and aggregation. Previously, we optimized PAL from R. toruloides, and in this case we reduced aggregation of the A. variabilis PAL by mutating two surface cysteine residues (C503 and C565) to serines. Additionally, we report the structural and biochemical characterization of the A. variabilis PAL C503S/C565S double mutant and carefully compare this molecule with the R. toruloides engineered PAL molecule. Unlike previously published PAL structures, significant electron density is observed for the two active-site loops in the A. variabilis C503S/C565S double mutant, yielding a complete view of the active site. Docking studies and N-hydroxysuccinimide-biotin binding studies support a proposed mechanism in which the amino group of the phenylalanine substrate is attacked directly by the 4-methylidene-imidazole-5-one prosthetic group. We propose a helix-to-loop conformational switch in the helices flanking the inner active-site loop that regulates accessibility of the active site. Differences in loop stability among PAL homologs may explain the observed variation in enzyme efficiency, despite the highly conserved structure of the active site. A. variabilis C503S/C565S PAL is shown to be both more thermally stable and more resistant to proteolytic cleavage than R. toruloides PAL. Additional increases in thermal stability and protease resistance upon ligand binding may be due to enhanced interactions among the residues of the active site, possibly locking the active-site structure in place and stabilizing the tetramer. Examination of the A. variabilis C503S/C565S PAL structure, combined with analysis of its physical properties, provides a structural basis for further engineering of residues that could result in a better therapeutic molecule.
- Published
- 2008
- Full Text
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7. A structural perspective of the sequence variability within botulinum neurotoxin subtypes A1-A4.
- Author
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Arndt JW, Jacobson MJ, Abola EE, Forsyth CM, Tepp WH, Marks JD, Johnson EA, and Stevens RC
- Subjects
- Amino Acid Sequence, Binding Sites, Conserved Sequence, Gangliosides metabolism, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Sequence Alignment, Synaptosomal-Associated Protein 25 chemistry, Botulinum Toxins, Type A chemistry, Clostridium botulinum chemistry
- Abstract
Botulinum neurotoxin (BoNT) is a category A toxin that has been classified within seven serotypes, designated A-G. Recently, it has been discovered that sequence variability occurs in BoNTs produced by serotype A (BoNT/A) variant strains, designated as subtypes A1 and A2, which have significantly different antibody-binding properties. We have therefore made efforts to understand at the molecular level the diversity and its effects on the biological actions of the toxin, including receptor binding, substrate recognition, and catalysis. We provide the results of these studies, including the analysis of two newly sequenced BoNT/A variants, Loch Maree (A3) and 657Ba (A4), and their comparison to A1 and A2. Using sequence analysis, available functional data, molecular modeling, and comparison of models with the crystal structures of BoNT/A1 and the light chain of BoNT/A2, we conclude that these sequence differences within subtypes will impact development of broad-spectrum antibody and small ligand therapeutics, and suggest dissimilarities in binding affinity and cleavage efficiency of the SNAP-25 substrate. In particular, sequence variation in subtypes BoNT/A3 and BoNT/A4 will likely effect alpha-exosite and S1' subsite recognition, respectively.
- Published
- 2006
- Full Text
- View/download PDF
8. Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
- Author
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Erlandsen H, Abola EE, and Stevens RC
- Subjects
- Binding Sites, Catecholamines metabolism, Enzymes chemistry, Glycolysis, Protein Conformation, Enzymes metabolism, Genome
- Abstract
An important goal of structural genomics is to complete the structural analysis of all the enzymes in metabolic pathways and to understand the structural similarities and differences. A preliminary glimpse of this type of analysis was achieved before structural genomics efforts with the glycolytic pathway and efforts are underway for many other pathways, including that of catecholamine metabolism. Structural enzymology necessitates a complete structural characterization, even for highly homologous proteins (greater than 80% sequence homology), as every active site has distinct structural features and it is these active site differences that distinguish one enzyme from another. Short cuts with homology modeling cannot be taken with our current knowledge base. Each enzyme structure in a pathway needs to be determined, including structures containing bound substrates, cofactors, products and transition state analogs, in order to obtain a complete structural and functional understanding of pathway-related enzymes.
- Published
- 2000
- Full Text
- View/download PDF
9. AutoDep: a web-based system for deposition and validation of macromolecular structural -information.
- Author
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Lin D, Manning NO, Jiang J, Abola EE, Stampf D, Prilusky J, and Sussman JL
- Subjects
- Computer Security, User-Computer Interface, Vocabulary, Database Management Systems, Internet, Macromolecular Substances
- Abstract
This paper describes the design and full implementation of a new concept in data deposition and validation: AutoDep (copyright Brookhaven Science Associates LLC). AutoDep changes the traditional procedure for data acceptance and validation of the primary databases into an interactive depositor-driven operation which almost eliminates the delay between the acceptance of the data and its public release. The system takes full advantage of the knowledge and expertise of the experimenters, rather than relying on the database curators for the complete and accurate description of the structural experiment and its results. AutoDep, developed by the Protein Data Bank at Brookhaven National Laboratory (BNL) as a flexible and portable system, has already been adopted by other primary databases and implemented on different platforms/operating systems. AutoDep was introduced at BNL in 1996 [see Manning (1996), Protein Data Bank Quart. Newslett. 77, 2 (ftp://ftp.rcsb. org/pub/pdb/doc/newsletters/bnl/newsletter96jul/newslttr+ ++.txt); Manning (1996), Protein Data Bank Quart. Newslett. 78, 2 (ftp://ftp. rcsb.org/pub/pdb/doc/newsletters/bnl/newsletter96oct/+ ++newslttr.txt)].
- Published
- 2000
- Full Text
- View/download PDF
10. Automated analysis of interatomic contacts in proteins.
- Author
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Sobolev V, Sorokine A, Prilusky J, Abola EE, and Edelman M
- Subjects
- Automation, Proteins metabolism, Proteins chemistry, Software
- Abstract
Motivation: New software has been designed to assist the molecular biologist in understanding the structural consequences of modifying a ligand and/or protein., Results: Tools are described for the analysis of ligand-protein contacts (LPC software) and contacts of structural units (CSU software) such as helices, sheets, strands and residues. Our approach is based on a detailed analysis of interatomic contacts and interface complementarity. For any ligand or structural unit, these software automatically: (i) calculate the solvent-accessible surface of every atom; (ii) determine the contacting residues and type of interaction they undergo (hydrophobic-hydrophobic, aromatic-aromatic, etc.); (iii) indicate all putative hydrogen bonds. LPC software further predicts changes in binding strength following chemical modification of the ligand., Availability: Both LPC and CSU can be accessed through the PDB and are integrated in the 3DB Atlas page of all PDB files. For any given file, the tools can also be accessed at http://www.pdb.bnl. gov/pdb-bin/lpc?PDB_ID= and http://www.pdb.bnl. gov/pdb-bin/csu?PDB_ID= with the four-letter PDB code added at the end in each case. Finally, LPC and CSU can be accessed at: http://sgedg.weizmann.ac.il/lpc and http://sgedg.weizmann.ac.il/csu.
- Published
- 1999
- Full Text
- View/download PDF
11. The protein data bank. Bridging the gap between the sequence and 3D structure world.
- Author
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Sussman JL, Abola EE, Lin D, Jiang J, Manning NO, and Prilusky J
- Subjects
- History, 20th Century, Internet, United States, Databases, Factual history, Proteins chemistry, Sequence Analysis, Protein history
- Abstract
The protein data bank (PDB), at Brookhaven National Laboratory, is a database containing information on experimentally determined three-dimensional structures of proteins, nucleic acids, and other biological macromolecules, with approximately 9000 entries. The PDB has a 27-year history of service to a global community of researchers, educators, and students in a wide variety of scientific disciplines. Data are easily submitted via PDB's WWW-based tool AutoDep, in either PDB or mmCIF format, and are most conveniently examined via PDB's WWW-based tool 3DB Browser. Collaborative centers have been, and continue to be, established worldwide to assist in data deposition, archiving, and distribution.
- Published
- 1999
- Full Text
- View/download PDF
12. Protein Data Bank (PDB): database of three-dimensional structural information of biological macromolecules.
- Author
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Sussman JL, Lin D, Jiang J, Manning NO, Prilusky J, Ritter O, and Abola EE
- Subjects
- Database Management Systems, Databases, Factual, Protein Conformation
- Abstract
The Protein Data Bank (PDB) at Brookhaven National Laboratory, is a database containing experimentally determined three-dimensional structures of proteins, nucleic acids and other biological macromolecules, with approximately 8000 entries. Data are easily submitted via PDB's WWW-based tool AutoDep, in either mmCIF or PDB format, and are most conveniently examined via PDB's WWW-based tool 3DB Browser.
- Published
- 1998
- Full Text
- View/download PDF
13. Protein Data Bank archives of three-dimensional macromolecular structures.
- Author
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Abola EE, Sussman JL, Prilusky J, and Manning NO
- Subjects
- Amino Acid Sequence, Carbohydrates chemistry, Crystallography, X-Ray methods, Nucleic Acids chemistry, Nucleoproteins chemistry, Peptides chemistry, Protein Structure, Secondary, Reproducibility of Results, Software, Databases, Factual, Protein Conformation, Proteins chemistry
- Published
- 1997
- Full Text
- View/download PDF
14. Errors in protein structures.
- Author
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Hooft RW, Vriend G, Sander C, and Abola EE
- Subjects
- Crystallography, X-Ray, Databases, Factual, Quality Control, Protein Conformation
- Published
- 1996
- Full Text
- View/download PDF
15. The Protein Data Bank: Current Status and Future Challenges.
- Author
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Abola EE, Manning NO, Prilusky J, Stampf DR, and Sussman JL
- Abstract
The Protein Data Bank (PDB) is an archive of experimentally determined three-dimensional structures of proteins, nucleic acids, and other biological macromolecules with a 25 year history of service to a global community. PDB is being replaced by 3DB, the Three-Dimensional Database of Biomolecular Structures that will continue to operate from Brookhaven National Laboratory. 3DB will be a highly sophisticated knowledge-based system for archiving and accessing structural information that combines the advantages of object oriented and relational database systems. 3DB will operate as a direct-deposition archive that will also accept third-party supplied annotations. Conversion of PDB to 3DB will be evolutionary, providing a high degree of compatibility with existing software.
- Published
- 1996
- Full Text
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16. Designing medical informatics research and library--resource projects to increase what is learned.
- Author
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Stead WW, Haynes RB, Fuller S, Friedman CP, Travis LE, Beck JR, Fenichel CH, Chandrasekaran B, Buchanan BG, and Abola EE
- Subjects
- Evaluation Studies as Topic, Libraries, Research, Research Design, Research Support as Topic, Medical Informatics
- Abstract
Careful study of medical informatics research and library-resource projects is necessary to increase the productivity of the research and development enterprise. Medical informatics research projects can present unique problems with respect to evaluation. It is not always possible to adapt directly the evaluation methods that are commonly employed in the natural and social sciences. Problems in evaluating medical informatics projects may be overcome by formulating system development work in terms of a testable hypothesis; subdividing complex projects into modules, each of which can be developed, tested and evaluated rigorously; and utilizing qualitative studies in situations where more definitive quantitative studies are impractical.
- Published
- 1994
- Full Text
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17. Marked structural differences of the Mcg Bence--Jones dimer in two crystal systems.
- Author
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Abola EE, Ely KR, and Edmundson AB
- Subjects
- Crystallization, Humans, Macromolecular Substances, Models, Molecular, Protein Conformation, X-Ray Diffraction, Bence Jones Protein urine
- Published
- 1980
- Full Text
- View/download PDF
18. Three-dimensional structure of the Mcg IgG1 immunoglobulin.
- Author
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Rajan SS, Ely KR, Abola EE, Wood MK, Colman PM, Athay RJ, and Edmundson AB
- Subjects
- Computers, Crystallization, Humans, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, X-Ray Diffraction, Immunoglobulin G, Immunoglobulin Light Chains, Immunoglobulin lambda-Chains, Models, Structural
- Abstract
The three-dimensional structure of an IgG1(lambda) immunoglobulin from a patient (Mcg) with amyloidosis was determined at 6.5-A resolution with X-ray diffraction techniques. The protein crystallized from water in the space group C2221, with a = 87.8, b = 111.3 and c = 186.3 A; the crystallographic asymmetric unit was a half-molecule consisting of one light and one heavy chain. The structure was solved by the multiple isomorphous replacement method with five heavy-atom derivatives. Electron density maps were interpreted with the aid of a protein modeling system used in conjunction with an Evans and Sutherland Picture System II graphics station. IgG1 molecules were tightly packed in the crystal lattice, with numerous intermolecular contacts. The two-fold axis relating identical halves of each molecule was found to be parallel to the y crystallographic axis. Electron density modules collectively representing one molecule were identified as three lobes representing the two antigen-binding (Fab) arms and the Fc region. An interchain disulfide bond connecting the two CL domains was located on the molecular diad and used as a landmark in the interpretation of the electron density map. A computer graphics method was developed to produce a solid image model of the IgG1 molecule in any prescribed orientation.
- Published
- 1983
- Full Text
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19. Mobile Fc region in the Zie IgG2 cryoglobulin: comparison of crystals of the F(ab')2 fragment and the intact immunoglobulin.
- Author
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Ely KR, Colman PM, Abola EE, Hess AC, Peabody DS, Parr DM, Connell GE, Laschinger CA, and Edmundson AB
- Subjects
- Humans, Protein Conformation, Structure-Activity Relationship, X-Ray Diffraction, Cryoglobulins, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Immunoglobulin G, Myeloma Proteins
- Published
- 1978
- Full Text
- View/download PDF
20. Binding of 2,4-dinitrophenyl compounds and other small molecules to a crystalline lambda-type Bence-Jones dimer.
- Author
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Edmundson AB, Ely KR, Girling RL, Abola EE, Schiffer M, Westholm FA, Fausch MD, and Deutsch HF
- Subjects
- Amino Acid Sequence, Amino Acids metabolism, Binding Sites, Caffeine metabolism, Chemical Phenomena, Chemistry, Colchicine metabolism, Dansyl Compounds metabolism, Fluorine metabolism, Humans, Immunoglobulin Fragments, Iodine metabolism, Macromolecular Substances, Methadone metabolism, Models, Structural, Morphine metabolism, Phenanthrolines metabolism, Protein Binding, Protein Conformation, Uracil metabolism, Vitamin K metabolism, X-Ray Diffraction, Amyloidosis metabolism, Bence Jones Protein metabolism, Immunoglobulins metabolism, Nitrobenzenes metabolism
- Published
- 1974
- Full Text
- View/download PDF
21. Unexpected similarities in the crystal structures of the Mcg light-chain dimer and its hybrid with the Weir protein.
- Author
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Ely KR, Wood MK, Rajan SS, Hodsdon JM, Abola EE, Deutsch HF, and Edmundson AB
- Subjects
- Amino Acid Sequence, Binding Sites, Chemical Phenomena, Chemistry, Crystallization, Fourier Analysis, Models, Molecular, Protein Multimerization, X-Ray Diffraction, Immunoglobulin Light Chains, Immunoglobulin lambda-Chains
- Abstract
The covalently linked hybrid of two human lambda-type light chains (Mcg and Weir) crystallizes as trigonal bipyramids in ammonium sulfate [Ely et al., Molec. Immun. 22, 85-92 (1985)]. While markedly different in appearance from the barrel-shaped crystals of the parental Mcg dimer, the bipyramids of the hybrid have the same space group: trigonal P3(1)21. Moreover, the unit cell dimensions are practically identical: a = 72.3 A in both proteins; c = 188.1 A in the hybrid and 185.9 A in the Mcg dimer. These observations imply that the crystal packing and the main features of the three-dimensional structures are closely similar in the Mcg X Weir hybrid and the Mcg dimer. The "constant" domains of the Mcg and Weir proteins belong to the same genetic subclass and were expected to interact in comparable ways in hybrids and parental dimers. However, the overall similarities in the "variable" domain pairs in the hybrid and Mcg dimer were completely unpredicted, since the amino acid sequences of the heterologous variable domains differ by 36 residues. By difference Fourier analysis the Weir light chain has been tentatively identified as monomer 1 (heavy-chain analogue) and the Mcg protein as monomer 2 (light-chain analogue) in the hybrid dimer. Substitutions in key positions in the hypervariable loops explain the differences in binding activity of the Mcg and Weir dimers. In the Mcg dimer bis(dinitrophenyl)lysine spans two relatively spacious subsites (A and B), with primary contacts involving tyrosines 34 and 38 of monomer 2. The Weir dimer, which does not bind dinitrophenyl ligands, has serine and phenylalanine in homologous positions. Moreover, the bilateral replacement of valine 48 and serine 91 in Mcg by leucine and methionine in the Weir dimer should effectively block access to subsite B. In the hybrid binding activity for bis(dinitrophenyl)lysine is restored because the Mcg light chain is present as the monomer 2 subunit.
- Published
- 1985
- Full Text
- View/download PDF
22. Conformational isomerism, rotational allomerism, and divergent evolution in immunoglobulin light chains.
- Author
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Edmundson AB, Ely KR, Abola EE, Schiffer M, Panagiotopoulos N, and Deutsch HF
- Subjects
- Amino Acid Sequence, Humans, Immunoglobulin Fab Fragments, Models, Structural, Protein Conformation, Biological Evolution, Immunoglobulin G, Immunoglobulin Light Chains, Myeloma Proteins
- Abstract
Immunoglobulin light chains are examples of single polypeptide chains synthesized under the control of two genes. The three-dimensional structure of a human (Mcg) lambda-type chain (Bence-Jones) dimer supports the hypothesis of a common primordial gene for the amino ("variable" or V) and carboxyl ("constant" or C) halves of each monomer. However, sequence homologies have been obscurred by divergent evolution of the V and C regions ("domains"). The types of evolutionary changes that have occurred in the domain can be surmised by a comparison of the sequences, using the three-dimensional structures as a basis for alignment. Despite substantial differences in sequences, the hydrophobic character of key internal sites has been maintained in each domain. Regions present in only one domain are situated in position appropriate for their functions, but not deleterious to the general structural integrity of a common fold. The divergence of the V and C domains can be interpreted in terms of rotational allomerism. The cylinders of beta-pleated sheets have rotated in such a way that homologous regions in the two domains perform different functions in their interactions with a second molecule of light or heavy chain. These regions include complementarity-determining sites for antigen binding in the V domains and crossover sites stabilizing dimer formation in the C domains. Differences in surface properties between the V1-V2 and C1-C2 dimeric modules may partially explain why the V regions have been implicated in the formation of amyloid fibrils and in the characteristic thermal behavior of Bence-Jones proteins.
- Published
- 1976
23. Crystal properties as indicators of conformational changes during ligand binding or interconversion of Mcg light chain isomers.
- Author
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Ely KR, Firca JR, Williams KJ, Abola EE, Fenton JM, Schiffer M, Panagiotopoulos NC, and Edmundson AB
- Subjects
- Bence Jones Protein, Humans, Macromolecular Substances, Models, Molecular, Protein Conformation, X-Ray Diffraction, Immunoglobulin G, Immunoglobulin Light Chains
- Published
- 1978
- Full Text
- View/download PDF
24. Conformational flexibility in immunoglobulins.
- Author
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Edmundson AB, Ely KR, and Abola EE
- Subjects
- Antigen-Antibody Complex, Bence Jones Protein immunology, Chromosome Deletion, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Immunoglobulin G, Immunoglobulin Light Chains, Models, Molecular, Motion, Protein Conformation, X-Ray Diffraction, Immunoglobulins genetics, Myeloma Proteins genetics
- Published
- 1978
- Full Text
- View/download PDF
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