Variations in Antigen−Antibody Association Kinetics as a Function of pH and Salt Concentration: A QSAR and Molecular Modeling Study
| Autor: | Danièle Altschuh, Laurence Choulier, Erwin De Genst, Virginie Lafont, Annick Dejaegere |
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| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Cellular and Molecular Immunology, Vrije Universiteit Brussel, Klotz, Evelyne |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular MESH: Hydrogen-Ion Concentration Molecular model [SDV]Life Sciences [q-bio] Molecular binding Quantitative Structure-Activity Relationship Antigen-Antibody Complex 01 natural sciences Biochemistry Models MESH: Animals Salts/*chemistry Non-U.S. Gov't ComputingMilieux_MISCELLANEOUS MESH: Quantitative Structure-Activity Relationship 0303 health sciences Antibodies/*chemistry/genetics/metabolism Chemistry Antigens/*chemistry/genetics/metabolism Temperature MESH: Antigen-Antibody Complex Hydrogen-Ion Concentration MESH: Temperature Receptor–ligand kinetics MESH: Salts MESH: Antigens Titration MESH: Models Molecular Muramidase/chemistry/genetics/metabolism Protein Binding Quantitative structure–activity relationship Kinetics Thermodynamics Research Support 010402 general chemistry MESH: Multivariate Analysis Antibodies 03 medical and health sciences MESH: Protein Binding Animals Antigens 030304 developmental biology MESH: Antibodies Solvation Molecular [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology 0104 chemical sciences Crystallography Ionic strength MESH: Muramidase Multivariate Analysis Muramidase Salts Antigen-Antibody Complex/*chemistry |
| Zdroj: | Biochemistry Biochemistry, American Chemical Society, 2005, 44 (44), pp.14409-14418. ⟨10.1021/bi050986v⟩ Biochemistry, American Chemical Society, 2005, 44, pp.14409-18 Biochemistry, American Chemical Society, 2005, 44 (44), pp.14409-18. ⟨10.1021/bi050986v⟩ |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi050986v |
| Popis: | 0006-2960 (Print) Journal Article; The relationship between three environmental factors (ionic strength, pH, and temperature) and antigen-antibody binding kinetics was investigated using QSAR (quantitative structure-activity relationship) and molecular modeling approaches. The interaction used for this analysis is that between the camel antibody fragment cAbLys3 and lysozyme. Binding kinetics were measured using a Biacore 2000 instrument, at NaCl concentrations between 50 and 500 mM, at pH's between 5 and 10, and at temperatures between 15 and 30 degrees C, according to multivariate experimental designs. Variations in kinetic on- and off-rate parameters were up to 400- and 16-fold, respectively. Mathematical models that relate log k(on) to experimental conditions were developed. They indicated an influence of all three factors, with a clear dependency between pH and NaCl concentration for their effect on k(on). These models were able to predict on-rate parameters under new experimental conditions. Titration calculations using continuum electrostatics were performed on the crystallographic structures of the isolated and bound proteins to gain structural insight for the on-rate enhancement observed at pH |
| Databáze: | OpenAIRE |
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