1j2l | pdb_00001j2l

Crystal structure of the disintegrin, trimestatin

spinqualitylabelsall models 1j2l, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1j2l is a 1 chain structure with sequence from Trimeresurus flavoviridis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [VM2T_PROFL] Inhibits fibrinogen interaction with platelets. Acts by binding to alpha-IIb/beta-3 (ITGA2B/ITGB3) on the platelet surface and inhibits aggregation induced by ADP, thrombin, platelet-activating factor and collagen. 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 Disintegrins are a family of small proteins containing an Arg-Gly-Asp (RGD) sequence motif that binds specifically to integrin receptors. Since the integrin is known to serve as the final common pathway leading to aggregation via formation of platelet-platelet bridges, disintegrins act as fibrinogen receptor antagonists. Here, we report the first crystal structure of a disintegrin, trimestatin, found in snake venom. The structure of trimestatin at 1.7A resolution reveals that a number of turns and loops form a rigid core stabilized by six disulfide bonds. Electron densities of the RGD sequence are visible clearly at the tip of a hairpin loop, in such a manner that the Arg and Asp side-chains point in opposite directions. A docking model using the crystal structure of integrin alphaVbeta3 suggests that the Arg binds to the propeller domain, and Asp to the betaA domain. This model indicates that the C-terminal region is another potential binding site with integrin receptors. In addition to the RGD sequence, the structural evidence of a C-terminal region (Arg66, Trp67 and Asn68) important for disintegrin activity allows understanding of the high affinity and selectiveness of snake venom disintegrin for integrin receptors. The crystal structure of trimestatin should provide a useful framework for designing and developing more effective drugs for controlling platelet aggregation and anti-angiogenesis cancer. Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD.,Fujii Y, Okuda D, Fujimoto Z, Horii K, Morita T, Mizuno H J Mol Biol. 2003 Oct 3;332(5):1115-22. PMID:14499613 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Disintegrin

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