3c05
From Proteopedia
Crystal structure of Acostatin from Agkistrodon Contortrix Contortrix
Structural highlights
Function[DIDA_AGKCO] Inhibits fibrinogen interaction with platelets. Acts by binding to alpha-IIb/beta-3 (ITGA2B/ITGB3) on the platelet surface and inhibits ADP-induced platelet aggregation in human platelet-rich plasma.[1] [VM2AB_AGKCO] Snake venom metalloproteinase: impairs hemostasis in the envenomed animal (By similarity). This product has not been identified in the venom. Disintegrin acostatin-beta: inhibits platelet aggregation in human platelet-rich plasma induced by ADP. Acts by inhibiting fibrinogen interaction with platelet receptors GPIIb/GPIIIa (ITGA2B/ITGB3). 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 PubMedDisintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an alphabeta heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R(work) and R(free) of 18.6% and 21.5%, respectively, using all data in the 20-1.7 A resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short beta-sheets, each of which is formed by a pair of antiparallel beta-strands connected by beta-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the alphabeta chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an alphabetabetaalpha acostatin tetramer. Further experiments are required to identify whether the alphabetabetaalpha acostatin complex plays a functional role in vivo. Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution.,Moiseeva N, Bau R, Swenson SD, Markland FS Jr, Choe JY, Liu ZJ, Allaire M Acta Crystallogr D Biol Crystallogr. 2008 Apr;64(Pt 4):466-70. Epub 2008, Mar 19. PMID:18391413[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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