1iqd
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(New page: 200px<br /> <applet load="1iqd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iqd, resolution 2.00Å" /> '''Human Factor VIII C...)
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Revision as of 15:26, 12 November 2007
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Human Factor VIII C2 Domain complexed to human monoclonal BO2C11 Fab.
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Hemophilia A OMIM:[306700]
About this Structure
1IQD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII., Spiegel PC Jr, Jacquemin M, Saint-Remy JM, Stoddard BL, Pratt KP, Blood. 2001 Jul 1;98(1):13-9. PMID:11418455
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