1IQD
Human Factor VIII C2 Domain complexed to human monoclonal BO2C11 Fab.
Summary for 1IQD
Entry DOI | 10.2210/pdb1iqd/pdb |
Related | 1D7P |
Descriptor | HUMAN MONOCLONAL BO2C11 FAB LIGHT CHAIN, HUMAN MONOCLONAL BO2C11 FAB HEAVY CHAIN, HUMAN FACTOR VIII, ... (4 entities in total) |
Functional Keywords | factor viii, c2 domain, antibody, blood coagulation, inhibitor, bo2c11, immune system-blood clotting complex, immune system/blood clotting |
Biological source | Homo sapiens (human) More |
Cellular location | Secreted, extracellular space: P00451 |
Total number of polymer chains | 3 |
Total formula weight | 63403.13 |
Authors | Spiegel Jr., P.C.,Jacquemin, M.,Saint-Remy, J.M.,Stoddard, B.L.,Pratt, K.P. (deposition date: 2001-07-21, release date: 2001-08-15, Last modification date: 2024-10-30) |
Primary citation | Spiegel Jr., P.C.,Jacquemin, M.,Saint-Remy, J.M.,Stoddard, B.L.,Pratt, K.P. Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII. Blood, 98:13-19, 2001 Cited by PubMed Abstract: 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. PubMed: 11418455DOI: 10.1182/blood.V98.1.13 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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