1iqd
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The development of an immune response to infused factor VIII is a | + | 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== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jacquemin, M.]] | [[Category: Jacquemin, M.]] | ||
| - | [[Category: Jr., P | + | [[Category: Jr., P C.Spiegel.]] |
| - | [[Category: Pratt, K | + | [[Category: Pratt, K P.]] |
| - | [[Category: Saint-Remy, J | + | [[Category: Saint-Remy, J M.]] |
| - | [[Category: Stoddard, B | + | [[Category: Stoddard, B L.]] |
[[Category: antibody]] | [[Category: antibody]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
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[[Category: inhibitor]] | [[Category: inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:14:26 2008'' |
Revision as of 11:14, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 13:14:26 2008
