Structural analysis of an anti-estradiol antibody
Author
Summary, in English
An anti-estradiol antibody with improved specificity is searched for by combining steroid analog binding studies, mutant antibodies obtained from a phage-display library and structural modeling. Three-dimensional models for the anti-estradiol antibody 57-2 were constructed by comparative model building. Estradiol and analogs were docked into the combining site and molecular dynamics simulation was used to further refine this area of the protein. Cross-reactivities measured against 36 steroid analogs were used to help in the docking process and to evaluate the models. The roles of a number of residues were assessed by characterization of cross-reactivity mutants obtained from a phage display library. The cross-reactivity data and the results observed for mutants are explained by the structural model, in which the estradiol D-ring inserts deeply into the binding site and interacts with the antibody through at least one specific hydrogen bond. The binding data strongly suggest that this hydrogen bond connects the estradiol 17-hydroxyl group with the side chain of Gin H35. As expected for the binding of a small aromatic molecule, the antibody binding site contains many aromatic residues, e.g. Trp H50, H95 and L96 and Tyr L32, L49 and Phe L91. (C) 1997 Published by Elsevier Science Ltd. All rights reserved.
Publishing year
1997
Language
English
Pages
1215-1226
Publication/Series
Molecular Immunology
Volume
34
Issue
16-17
Document type
Journal article
Publisher
Pergamon Press Ltd.
Topic
- Immunology in the medical area
Keywords
- protein modeling
- antibody
- steroid
- estradiol
- cross-reactivity
- protein engineering
- antibody-antigen interactions
Status
Published
ISBN/ISSN/Other
- ISSN: 1872-9142