Structural analysis of an anti-estradiol antibody
| Autor: | Bruno O. Villoutreix, Lennart Nilsson, Petri Saviranta, Mauno Vihinen, Urpo Lamminmäki, Piitu Jauria, Olle Teleman, Timo Lövgren |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Phage display medicine.medical_treatment 030303 biophysics Immunology Molecular Sequence Data Protein Engineering Antibodies Steroid 03 medical and health sciences Mice Structure-Activity Relationship Antibody Specificity medicine Structure–activity relationship Animals Humans Amino Acid Sequence Binding site Molecular Biology Peptide sequence 030304 developmental biology 0303 health sciences Estradiol Genes Immunoglobulin Chemistry Protein engineering 3. Good health Biochemistry Docking (molecular) Sequence Analysis Steroid analog |
| Zdroj: | Molecular immunology. 34(16-17) |
| ISSN: | 0161-5890 |
| Popis: | 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 Gln 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. |
| Databáze: | OpenAIRE |
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