1d7x

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Current revision (06:50, 7 February 2024) (edit) (undo)
 
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<StructureSection load='1d7x' size='340' side='right'caption='[[1d7x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='1d7x' size='340' side='right'caption='[[1d7x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1d7x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D7X FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1d7x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D7X FirstGlance]. <br>
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</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=SPC:N-HYDROXY+1N(4-METHOXYPHENYL)SULFONYL-4-(Z,E-N-METHOXYIMINO)PYRROLIDINE-2R-CARBOXAMIDE'>SPC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cqr|1cqr]], [[1d5j|1d5j]]</div></td></tr>
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<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=SPC:N-HYDROXY+1N(4-METHOXYPHENYL)SULFONYL-4-(Z,E-N-METHOXYIMINO)PYRROLIDINE-2R-CARBOXAMIDE'>SPC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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/Stromelysin_1 Stromelysin 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </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=1d7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d7x OCA], [https://pdbe.org/1d7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d7x RCSB], [https://www.ebi.ac.uk/pdbsum/1d7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d7x 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=1d7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d7x OCA], [https://pdbe.org/1d7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d7x RCSB], [https://www.ebi.ac.uk/pdbsum/1d7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d7x ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN]] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM:[https://omim.org/entry/614466 614466]]. A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Note=A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.<ref>PMID:8662692</ref> <ref>PMID:12477941</ref>
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[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM:[https://omim.org/entry/614466 614466]. A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Note=A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.<ref>PMID:8662692</ref> <ref>PMID:12477941</ref>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN]] Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
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[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN] Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1d7x ConSurf].
</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=1d7x ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically &lt;10 nM for MMP-3 and &lt;100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.
 
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Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold.,Cheng M, De B, Almstead NG, Pikul S, Dowty ME, Dietsch CR, Dunaway CM, Gu F, Hsieh LC, Janusz MJ, Taiwo YO, Natchus MG, Hudlicky T, Mandel M J Med Chem. 1999 Dec 30;42(26):5426-36. PMID:10639284<ref>PMID:10639284</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1d7x" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Stromelysin 1]]
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[[Category: Almstead NG]]
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[[Category: Almstead, N G]]
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[[Category: Cheng MY]]
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[[Category: Cheng, M Y]]
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[[Category: De B]]
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[[Category: De, B]]
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[[Category: Natchus MG]]
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[[Category: Natchus, M G]]
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[[Category: Pikul S]]
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[[Category: Pikul, S]]
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[[Category: Hydrolase]]
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[[Category: Inhibited]]
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[[Category: Mixed alpha beta structure]]
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[[Category: Zinc protease]]
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Current revision

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.

PDB ID 1d7x

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