| Autor: |
Spiegel PC Jr; Graduate Program in Biomolecular Structure and Design, University of Washington, and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Jacquemin M, Saint-Remy JM, Stoddard BL, Pratt KP |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2001 Jul 01; Vol. 98 (1), pp. 13-9. |
| DOI: |
10.1182/blood.v98.1.13 |
| Abstrakt: |
The development of an immune response to infused factor VIII is a complication affecting many patients with hemophilia A. Inhibitor antibodies bind to antigenic determinants on the factor VIII molecule and block its procoagulant activity. A patient-derived inhibitory immunoglobulin G4kappa antibody (BO2C11) produced by an immortalized memory B-lymphocyte cell line interferes with the binding of factor VIII to phospholipid surfaces and to von Willebrand factor. The structure of a Fab fragment derived from this antibody complexed with the factor VIII C2 domain was determined at 2.0 A resolution. The Fab interacts with solvent-exposed basic and hydrophobic side chains that form a membrane-association surface of factor VIII. This atomic resolution structure suggests a variety of amino acid substitutions in the C2 domain of factor VIII that might prevent the binding of anti-C2 inhibitor antibodies without significantly compromising the procoagulant functions of factor VIII. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
