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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3c05]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Agkistrodon_contortrix_contortrix Agkistrodon contortrix contortrix]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C05 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3c05]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Agkistrodon_contortrix_contortrix Agkistrodon contortrix contortrix]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C05 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c05 OCA], [https://pdbe.org/3c05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c05 RCSB], [https://www.ebi.ac.uk/pdbsum/3c05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c05 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c05 OCA], [https://pdbe.org/3c05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c05 RCSB], [https://www.ebi.ac.uk/pdbsum/3c05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c05 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DIDA_AGKCO 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.<ref>PMID:12450389</ref> [[https://www.uniprot.org/uniprot/VM2AB_AGKCO 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).
| + | [https://www.uniprot.org/uniprot/DIDA_AGKCO 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.<ref>PMID:12450389</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Agkistrodon contortrix contortrix]] | | [[Category: Agkistrodon contortrix contortrix]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allaire, M]] | + | [[Category: Allaire M]] |
| - | [[Category: Bau, R]] | + | [[Category: Bau R]] |
| - | [[Category: Moiseeva, N]] | + | [[Category: Moiseeva N]] |
| - | [[Category: Beta-sheet]]
| + | |
| - | [[Category: Blood clotting-antitumor protein complex]]
| + | |
| - | [[Category: Blood coagulation]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Disulfide bridge]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zymogen]]
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| 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]
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 (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 Also
References
- ↑ Okuda D, Koike H, Morita T. A new gene structure of the disintegrin family: a subunit of dimeric disintegrin has a short coding region. Biochemistry. 2002 Dec 3;41(48):14248-54. PMID:12450389
- ↑ Moiseeva N, Bau R, Swenson SD, Markland FS Jr, Choe JY, Liu ZJ, Allaire M. Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2008 Apr;64(Pt 4):466-70. Epub 2008, Mar 19. PMID:18391413 doi:10.1107/S0907444908002370
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