1cvw

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spinqualitylabelsall models 1cvw, resolution 2.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF ACTIVE SITE-INHIBITED HUMAN COAGULATION FACTOR VIIA (DES-GLA)

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Factor VIIa (FVIIa) is a crucial haemostatic protease consisting of four, distinct domains termed the Gla, epidermal growth factor-1 (EGF-1), EGF-2, and protease domains (from N- to C-terminus). The crystal structure of, human FVIIa inhibited at the active site with 1, 5-dansyl-Glu-Gly-Arg-chloromethyl ketone and lacking the Gla domain has, been solved to a resolution of 2.28 A. The EGF-2 and protease domains were, well resolved, whereas no electron density for the EGF-1 domain was, observed, suggesting a flexible arrangement or disorder within the, crystal. Superposition of the protease domain of the present structure, with that previously resolved in the tissue factor (TF)/FVIIai complex, revealed that although overall the domain structures are similar, the, EGF-2 domain is rotated by 7.5 degrees relative to the protease domain on, binding TF. A single cleavage in the protease domain was found, between, Arg315 and Lys316 (chymotrypsin numbering 170C-170D) in a FVII-specific, insertion loop: this cleavage appeared to be essential for, crystallisation. Insertion of the heavy chain N-terminal Ile153 is, essentially identical in the two structures, as is the geometry of the, active site residues and the inhibitor C-terminal arginine residue. Some, differences are seen in the cleaved loop, but changes in TF-contact, residues are generally minor. This structure supports the hypothesis that, TF binding enables spatial domain arrangements in the flexible FVIIa, molecule necessary for procoagulant function and furthermore that active, site occupancy induces FVIIa active conformation via N-terminal insertion.

Disease

Known diseases associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]

About this Structure

1CVW is a Single protein structure of sequence from Homo sapiens with CA and ANS as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.

Reference

Crystal structure of active site-inhibited human coagulation factor VIIa (des-Gla)., Kemball-Cook G, Johnson DJ, Tuddenham EG, Harlos K, J Struct Biol. 1999 Oct;127(3):213-23. PMID:10544046

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