1qfk
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(New page: 200px<br /> <applet load="1qfk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qfk, resolution 2.800Å" /> '''STRUCTURE OF HUMAN...)
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Revision as of 16:46, 12 November 2007
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STRUCTURE OF HUMAN FACTOR VIIA AND ITS IMPLICATIONS FOR THE TRIGGERING OF BLOOD COAGULATION
Contents |
Overview
Factor VIIa (EC 3.4.21.21) is a trypsin-like serine protease that plays a, key role in the blood coagulation cascade. On injury, factor VIIa forms a, complex with its allosteric regulator, tissue factor, and initiates blood, clotting. Although the structure of the binary complex has already been, determined [Banner, D. W., D'Arcy, A., Chene, C., Winkler, F. K., Guha, A., Konigsberg, W. H., Nemerson, Y. & Kirchhofer, D. (1996) Nature, (London) 380, 41-46], the conformational effects of cofactor binding to, factor VIIa are not known in detail because of a lack of structural, information on free factor VIIa. Here we report the structure of, gamma-carboxyglutamic acid-domainless human coagulation factor VIIa at a, resolution of 2.8 A. The molecule adopts an extended conformation within, the crystal similar to that previously observed for the full-length, protein in complex with tissue factor. Detailed comparison of free and, tissue factor-bound factor VIIa reveals several structural differences., The binding mode of the active-site inhibitor D-Phe-Phe-Arg methyl ketone, differs in the two structures, suggesting a role for the cofactor in, substrate recognition. More importantly, a surface-exposed alpha-helix in, the protease domain (residues 307-312), which is located at the cofactor, recognition site, is distorted in the free form of factor VIIa. This, subtle structural difference sheds light on the mechanism of the dramatic, tissue factor-induced enhancement of factor VIIa activity.
Disease
Known diseases associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this Structure
1QFK is a Single protein structure of sequence from Homo sapiens with GLC, FUC, CA and CH2 as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.
Reference
Structure of human factor VIIa and its implications for the triggering of blood coagulation., Pike AC, Brzozowski AM, Roberts SM, Olsen OH, Persson E, Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8925-30. PMID:10430872
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