1j2l
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(New page: 200px<br /><applet load="1j2l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1j2l, resolution 1.70Å" /> '''Crystal structure of...)
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Revision as of 15:45, 20 November 2007
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Crystal structure of the disintegrin, trimestatin
Overview
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.
About this Structure
1J2L is a Single protein structure of sequence from Trimeresurus flavoviridis with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
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
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