Structural analysis of an anti-estradiol antibody
Lamminmaki, U ; Villoutreix, BO ; Jauria, P ; Saviranta, P ; Vihinen, Mauno LU
; Nilsson, L
; Teleman, O
and Lovgren, T
(1997)
In Molecular Immunology
34(16-17).
p.1215-1226
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3852770
- author
- Lamminmaki, U
; Villoutreix, BO
; Jauria, P
; Saviranta, P
; Vihinen, Mauno
LU
; Nilsson, L
; Teleman, O
and Lovgren, T
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- protein modeling, antibody, steroid, estradiol, cross-reactivity, protein engineering, antibody-antigen interactions
- in
- Molecular Immunology
- volume
- 34
- issue
- 16-17
- pages
- 1215 - 1226
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- wos:000072787000011
- scopus:0344701071
- ISSN
- 1872-9142
- DOI
- 10.1016/S0161-5890(97)00085-0
- language
- English
- LU publication?
- no
- id
- 23236916-85c4-4e0b-b813-d59527c50376 (old id 3852770)
- date added to LUP
- 2016-04-01 15:18:46
- date last changed
- 2022-01-28 04:43:13
@article{23236916-85c4-4e0b-b813-d59527c50376,
abstract = {{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.}},
author = {{Lamminmaki, U and Villoutreix, BO and Jauria, P and Saviranta, P and Vihinen, Mauno and Nilsson, L and Teleman, O and Lovgren, T}},
issn = {{1872-9142}},
keywords = {{protein modeling; antibody; steroid; estradiol; cross-reactivity; protein engineering; antibody-antigen interactions}},
language = {{eng}},
number = {{16-17}},
pages = {{1215--1226}},
publisher = {{Pergamon Press Ltd.}},
series = {{Molecular Immunology}},
title = {{Structural analysis of an anti-estradiol antibody}},
url = {{http://dx.doi.org/10.1016/S0161-5890(97)00085-0}},
doi = {{10.1016/S0161-5890(97)00085-0}},
volume = {{34}},
year = {{1997}},
}