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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1kug]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Protobothrops_mucrosquamatus Protobothrops mucrosquamatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KUG FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1kug]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Protobothrops_mucrosquamatus Protobothrops mucrosquamatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KUG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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]] 1.37Å</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=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kuf|1kuf]], [[1kui|1kui]], [[1kuk|1kuk]]</div></td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Atrolysin_E Atrolysin E], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.44 3.4.24.44] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kug OCA], [https://pdbe.org/1kug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kug RCSB], [https://www.ebi.ac.uk/pdbsum/1kug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kug 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=1kug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kug OCA], [https://pdbe.org/1kug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kug RCSB], [https://www.ebi.ac.uk/pdbsum/1kug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kug ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VM2T3_PROMU 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).<ref>PMID:8068721</ref> <ref>PMID:8193588</ref> 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).<ref>PMID:8068721</ref> <ref>PMID:8193588</ref>
| + | [https://www.uniprot.org/uniprot/VM2T3_PROMU 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).<ref>PMID:8068721</ref> <ref>PMID:8193588</ref> 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).<ref>PMID:8068721</ref> <ref>PMID:8193588</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ku/1kug_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ku/1kug_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atrolysin E]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Protobothrops mucrosquamatus]] | | [[Category: Protobothrops mucrosquamatus]] |
| - | [[Category: Chiou, S H]] | + | [[Category: Chiou SH]] |
| - | [[Category: Huang, K F]] | + | [[Category: Huang KF]] |
| - | [[Category: Ko, T P]] | + | [[Category: Ko TP]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Wang AHJ]] |
| - | [[Category: Alpha/beta protein]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| - | [[Category: Retro-binding manner]]
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| 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
Venoms from crotalid and viperid snakes contain several peptide inhibitors which regulate the proteolytic activities of their snake-venom metalloproteinases (SVMPs) in a reversible manner under physiological conditions. In this report, we describe the high-resolution crystal structures of a SVMP, TM-3, from Taiwan habu (Trimeresurus mucrosquamatus) cocrystallized with the endogenous inhibitors pyroGlu-Asn-Trp (pENW), pyroGlu-Gln-Trp (pEQW) or pyroGlu-Lys-Trp (pEKW). The binding of inhibitors causes some of the residues around the inhibitor-binding environment of TM-3 to slightly move away from the active-site center, and displaces two metal-coordinated water molecules by the C-terminal carboxylic group of the inhibitors. This binding adopts a retro-manner principally stabilized by four possible hydrogen bonds. The Trp indole ring of the inhibitors is stacked against the imidazole of His143 in the S-1 site of the proteinase. Results from the study of synthetic inhibitor analogues showed the primary specificity of Trp residue of the inhibitors at the P-1 site, corroborating the stacking effect observed in our structures. Furthermore, we have made a detailed comparison of our structures with the binding modes of other inhibitors including batimastat, a hydroxamate inhibitor, and a barbiturate derivative. It suggests a close correlation between the inhibitory activity of an inhibitor and its ability to fill the S-1 pocket of the proteinase. Our work may provide insights into the rational design of small molecules that bind to this class of zinc-metalloproteinases.
Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues.,Huang KF, Chiou SH, Ko TP, Wang AH Eur J Biochem. 2002 Jun;269(12):3047-56. PMID:12071970[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, Wang AH. Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues. Eur J Biochem. 2002 Jun;269(12):3047-56. PMID:12071970
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