| Автор | Patten, Phillip A. |
| Автор | Gray, Nathanael S. |
| Автор | Yang, Priscilla L. |
| Автор | Marks, Cara B. |
| Автор | Wedemayer, Gary J. |
| Автор | Boniface, J. Jay |
| Автор | Stevens, Raymond C. |
| Автор | Schultz, Peter G. |
| Дата выпуска | 1996 |
| dc.description | The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10<sup>4</sup>, primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k<sub>cat</sub>/K<sub>m</sub>, from 1.7 × 10<sup>2</sup> M<sup>−1</sup> min<sup>−1</sup> to 1.4 × 10<sup>4</sup> M<sup>−1</sup> min<sup>−1</sup>. The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that none of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry or limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody. |
| Формат | application.pdf |
| Издатель | American Association for the Advancement of Science |
| Копирайт | © 1996 American Association for the Advancement of Science |
| Тема | Research Articles |
| Название | The Immunological Evolution of Catalysis |
| Тип | other |
| DOI | 10.1126/science.271.5252.1086 |
| Electronic ISSN | 1095-9203 |
| Print ISSN | 0036-8075 |
| Журнал | Science |
| Том | 271 |
| Первая страница | 1086 |
| Последняя страница | 1091 |
| Аффилиация | Patten Phillip A.; P. A. Patten, N. S. Gray, P. L. Yang, and P. G. Schultz are in the Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Gray Nathanael S.; P. A. Patten, N. S. Gray, P. L. Yang, and P. G. Schultz are in the Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Yang Priscilla L.; P. A. Patten, N. S. Gray, P. L. Yang, and P. G. Schultz are in the Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Marks Cara B.; C. B. Marks, G. J. Wedemayer, and R. C. Stevens are in the Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Wedemayer Gary J.; C. B. Marks, G. J. Wedemayer, and R. C. Stevens are in the Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Boniface J. Jay; J. J. Boniface is in the Howard Hughes Medical Institute, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. |
| Аффилиация | Stevens Raymond C.; C. B. Marks, G. J. Wedemayer, and R. C. Stevens are in the Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Аффилиация | Schultz Peter G.; P. A. Patten, N. S. Gray, P. L. Yang, and P. G. Schultz are in the Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA. |
| Выпуск | 5252 |
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