View source for 1hov


==SOLUTION STRUCTURE OF A CATALYTIC DOMAIN OF MMP-2 COMPLEXED WITH SC-74020==
<StructureSection load='1hov' size='340' side='right'caption='[[1hov]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hov]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HOV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=I52:N-{4-[(1-HYDROXYCARBAMOYL-2-METHYL-PROPYL)-(2-MORPHOLIN-4-YL-ETHYL)-SULFAMOYL]-4-PENTYL-BENZAMIDE'>I52</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1hov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hov OCA], [https://pdbe.org/1hov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hov RCSB], [https://www.ebi.ac.uk/pdbsum/1hov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hov ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:[https://omim.org/entry/259600 259600]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.<ref>PMID:11431697</ref> <ref>PMID:15691365</ref> <ref>PMID:16542393</ref> 
== Function ==
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>   PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>   Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</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/ho/1hov_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1hov ConSurf].
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== Publication Abstract from PubMed ==
MMP-2 is a member of the matrix metalloproteinase family that has been implicated in tumor cell metastasis and angiogenesis. Here, we describe the solution structure of a catalytic domain of MMP-2 complexed with a hydroxamic acid inhibitor (SC-74020), determined by three-dimensional heteronuclear NMR spectroscopy. The catalytic domain, designated MMP-2C, has a short peptide linker replacing the internal fibronectin-domain insertion and is enzymatically active. Distance geometry-simulated annealing calculations yielded 14 converged structures with atomic root-mean-square deviations (r.m.s.d.) of 1.02 and 1.62 A from the mean coordinate positions for the backbone and for all heavy atoms, respectively, when 11 residues at the N-terminus are excluded. The structure has the same global fold as observed for other MMP catalytic domains and is similar to previously solved crystal structures of MMP-2. Differences observed between the solution and the crystal structures, near the bottom of the S1' specificity loop, appear to be induced by the large inhibitor present in the solution structure. The MMP-2C solution structure is compared with MMP-8 crystal structure bound to the same inhibitor to highlight the differences especially in the S1' specificity loop. The finding provides a structural explanation for the selectivity between MMP-2 and MMP-8 that is achieved by large inhibitors.

Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor.,Feng Y, Likos JJ, Zhu L, Woodward H, Munie G, McDonald JJ, Stevens AM, Howard CP, De Crescenzo GA, Welsch D, Shieh HS, Stallings WC Biochim Biophys Acta. 2002 Jul 29;1598(1-2):10-23. PMID:12147339<ref>PMID:12147339</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 1hov" style="background-color:#fffaf0;"></div>

==See Also==
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: De Crescenzo GA]]
[[Category: Feng Y]]
[[Category: Howard CP]]
[[Category: Likos JJ]]
[[Category: McDonald JJ]]
[[Category: Munie G]]
[[Category: Shieh H-S]]
[[Category: Stallings WC]]
[[Category: Stevens AM]]
[[Category: Welsch D]]
[[Category: Woodward H]]
[[Category: Zhu L]]