View source for 1kug


==Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW==
<StructureSection load='1kug' size='340' side='right'caption='[[1kug]], [[Resolution|resolution]] 1.37&Aring;' scene=''>
== 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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.37&#8491;</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='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>
== 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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1kug ConSurf].
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== 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<ref>PMID:12071970</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1kug" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Protobothrops mucrosquamatus]]
[[Category: Chiou SH]]
[[Category: Huang KF]]
[[Category: Ko TP]]
[[Category: Wang AHJ]]