Structural highlights
Function
[VM2T3_PROMU] Snake venom metalloproteinase TM-3: fibrin(ogen)olytic protease which cleaves the Aalpha chain of fibrinogen (FGA) first followed by the Bbeta chain (FGB) and shows relatively low activity on the gamma chain (FGG).[1] [2] Disintegrin trimucrin: inhibits platelet aggregation induced by ADP, thrombin, platelet-activating factor and collagen. Acts by inhibiting fibrinogen interaction with platelet receptors GPIIb/GPIIIa (ITGA2B/ITGB3).[3] [4]
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 crystal structure of TM-3, a small snake-venom metalloproteinase (SVMP) isolated from Taiwan habu (Trimeresurus mucrosquamatus), was determined at 1.35 A resolution with resultant R and R(free) values of 0.181 and 0.204, respectively. The overall structure of TM-3 is an oblate ellipsoid that contains three disulfide crosslinks, Cys118-Cys197, Cys159-Cys181 and Cys161-Cys164. It exhibits the typical structural features of SVMPs and is closely related to the structure of the catalytic proteinase domain of TNFalpha-converting enzyme (TACE). In the present structure, the essential catalytic zinc ion was found to be replaced by a cadmium ion during crystallization, as revealed by atomic absorption analysis and X-ray data. This cadmium ion is bound to six ligands, including three conserved histidines and three water molecules, displaying the coordination geometry of a distorted octahedron. One of the water molecules is proposed to play the role of stabilizing the tetrahedral intermediate during the catalysis of SVMPs. The putative S'(1) specificity pocket of TM-3 is relatively shallow, in contrast to the deep pockets of adamalysin II, atrolysin C and H(2)-proteinase, but is similar to those in acutolysin A and TACE. The shallow pocket is a consequence of the presence of the non-conserved disulfide bond Cys159-Cys181 and the residue Gln174 at the bottom of the S'(1) pocket. The results indicate that the active-site structure of TM-3, among the know structures of SVMPs examined thus far, is most similar to that of TACE owing to their close disulfide configurations and the S'(1) specificity pocket.
The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium.,Huang KF, Chiou SH, Ko TP, Yuann JM, Wang AH Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1118-28. Epub 2002, Jun 20. PMID:12077431[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tsai IH, Wang YM, Lee YH. Characterization of a cDNA encoding the precursor of platelet aggregation inhibition and metalloproteinase from Trimeresurus mucrosquamatus venom. Biochim Biophys Acta. 1994 Aug 18;1200(3):337-40. PMID:8068721
- ↑ Huang KF, Hung CC, Chiou SH. Characterization of three fibrinogenolytic proteases isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem Mol Biol Int. 1993 Dec;31(6):1041-50. PMID:8193588
- ↑ Tsai IH, Wang YM, Lee YH. Characterization of a cDNA encoding the precursor of platelet aggregation inhibition and metalloproteinase from Trimeresurus mucrosquamatus venom. Biochim Biophys Acta. 1994 Aug 18;1200(3):337-40. PMID:8068721
- ↑ Huang KF, Hung CC, Chiou SH. Characterization of three fibrinogenolytic proteases isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem Mol Biol Int. 1993 Dec;31(6):1041-50. PMID:8193588
- ↑ Huang KF, Chiou SH, Ko TP, Yuann JM, Wang AH. The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium. Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1118-28. Epub 2002, Jun 20. PMID:12077431
