Conformational polymorphism of cyclosporin A
| العنوان: | Conformational polymorphism of cyclosporin A |
|---|---|
| المؤلفون: | Jean Claude Thierry, Malcolm D. Walkinshaw, Vincent Mikol, Kurt Wüthrich, Joerg Kallen, Danièle Altschuh, Olivier Vix, Werner Braun, Claus Spitzfaden |
| المساهمون: | Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Altschuh, Danièle, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Structure / Struct Fold Des; Structure (Camb ) Structure / Struct Fold Des; Structure (Camb ), 1994, 2 (10), pp.963-72 |
| بيانات النشر: | HAL CCSD, 1994. |
| سنة النشر: | 1994 |
| مصطلحات موضوعية: | Models, Molecular, Magnetic Resonance Spectroscopy, Protein Conformation, Molecular Conformation, Cypa, MESH: Peptidylprolyl Isomerase, MESH: Amino Acid Sequence, Crystallography, X-Ray, 01 natural sciences, MESH: Cyclosporine, Protein structure, MESH: Protein Conformation, Structural Biology, Cyclosporin a, Cyclophilin, Amino Acid Isomerases, 0303 health sciences, education.field_of_study, biology, Molecular Structure, Chemistry, MESH: State Medicine, Nuclear magnetic resonance spectroscopy, Peptidylprolyl Isomerase, Ligand (biochemistry), MESH: Immunoglobulin Fab Fragments, Cyclosporine, MESH: Laboratories, MESH: Great Britain, MESH: Models, Molecular, Protein Binding, Stereochemistry, Population, Molecular Sequence Data, MESH: Molecular Structure, MESH: Carrier Proteins, MESH: Amino Acid Isomerases, In Vitro Techniques, 010402 general chemistry, 03 medical and health sciences, Immunoglobulin Fab Fragments, MESH: Technology, Medical, MESH: Polymorphism, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH: Hydrogen Bonding, education, Molecular Biology, 030304 developmental biology, Peptidylprolyl isomerase, MESH: Molecular Conformation, Binding Sites, Polymorphism, Genetic, MESH: Humans, MESH: Molecular Sequence Data, MESH: Magnetic Resonance Spectroscopy, Hydrogen Bonding, biology.organism_classification, MESH: Crystallography, X-Ray, 0104 chemical sciences, MESH: Binding Sites, Carrier Proteins |
| الوصف: | Background: Cyclosporin A (CsA) is a cyclic undecapeptide fungal metabolite with immunosuppressive properties, widely used in transplant surgery. It forms a tight complex with the ubiquitous 18 kDa cytosolic protein cyclophilin A (CypA). The conformation of CsA in this complex, as studied by NMR or X-ray crystallography, is very different from that of free CsA. Another, different conformation of CsA has been found in a complex with an antibody fragment (Fab). Results A detailed comparison of the conformations of experimentally determined structures of protein-bound CsA is presented. The X-ray and NMR structures of CsA-CypA complexes are similar. The Fab-bound conformation of CsA, as determined by X-ray crystallography, is significantly different from the cyclophilin-bound conformation. The protein-CsA interactions in both the Fab and CypA complexes involve five hydrogen bonds, and the buried CsA surface areas are 395a and 300a, respectively. However, the CsA-protein interactions involve rather different side chain contacts in the two complexes. Conclusion The structural results presented here are consistent with CypA recognizing and binding a population of CsA molecules which are in the required CypA-binding conformation. In contrast, the X-ray structures of the Fab complex with CsA suggest that in this case there is mutual adaptation of both receptor and ligand during complex formation. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d56c90fb049f6654cd2d20ee52286c75 https://hal.archives-ouvertes.fr/hal-00265271 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....d56c90fb049f6654cd2d20ee52286c75 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |