1d7x: Difference between revisions
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<StructureSection load='1d7x' size='340' side='right'caption='[[1d7x]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='1d7x' size='340' side='right'caption='[[1d7x]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1d7x]] is a 2 chain structure with sequence from [ | <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> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | </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> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cqr|1cqr]], [[1d5j|1d5j]]</td></tr> | <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> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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 == | ||
[[ | [[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 == | ||
[[ | [[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]] | ||
| Line 34: | Line 34: | ||
==See Also== | ==See Also== | ||
*[[Matrix metalloproteinase|Matrix metalloproteinase]] | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 13:43, 14 July 2021
CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.
Structural highlights
Disease[MMP3_HUMAN] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM: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.[1] [2] Function[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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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 <10 nM for MMP-3 and <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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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