1jmj

Crystal Structure of Native Heparin Cofactor II

spinqualitylabelsall models 1jmj, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1jmj is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: BMA, CA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HEP2_HUMAN Defects in SERPIND1 are the cause of thrombophilia due to heparin cofactor 2 deficiency (THPH10) [MIM:612356. A hemostatic disorder characterized by a tendency to recurrent thrombosis. Function HEP2_HUMAN Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The serine proteases sequentially activated to form a fibrin clot are inhibited primarily by members of the serpin family, which use a unique beta-sheet expansion mechanism to trap and destroy their targets. Since the discovery that serpins were a family of serine protease inhibitors there has been controversy as to the role of conformational change in their mechanism. It now is clear that protease inhibition depends entirely on rapid serpin beta-sheet expansion after proteolytic attack. The regulatory advantage afforded by the conformational mobility of serpins is demonstrated here by the structures of native and S195A thrombin-complexed heparin cofactor II (HCII). HCII inhibits thrombin, the final protease of the coagulation cascade, in a glycosaminoglycan-dependent manner that involves the release of a sequestered hirudin-like N-terminal tail for interaction with thrombin. The native structure of HCII resembles that of native antithrombin and suggests an alternative mechanism of allosteric activation, whereas the structure of the S195A thrombin-HCII complex defines the molecular basis of allostery. Together, these structures reveal a multistep allosteric mechanism that relies on sequential contraction and expansion of the central beta-sheet of HCII. Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism.,Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11079-84. Epub 2002 Aug 8. PMID:12169660 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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