1d8m: Difference between revisions

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<StructureSection load='1d8m' size='340' side='right'caption='[[1d8m]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
<StructureSection load='1d8m' size='340' side='right'caption='[[1d8m]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1d8m]] 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=1D8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D8M FirstGlance]. <br>
<table><tr><td colspan='2'>[[1d8m]] 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=1D8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D8M FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBH:1-BENZYL-3-(4-METHOXY-BENZENESULFONYL)-6-OXO-HEXAHYDRO-PYRIMIDINE-4-CARBOXYLIC+ACID+HYDROXYAMIDE'>BBH</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.44&#8491;</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]], [[1d7x|1d7x]], [[1d8f|1d8f]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBH:1-BENZYL-3-(4-METHOXY-BENZENESULFONYL)-6-OXO-HEXAHYDRO-PYRIMIDINE-4-CARBOXYLIC+ACID+HYDROXYAMIDE'>BBH</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<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'>[https://proteopedia.org/fgij/fg.htm?mol=1d8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d8m OCA], [https://pdbe.org/1d8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d8m RCSB], [https://www.ebi.ac.uk/pdbsum/1d8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d8m 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=1d8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d8m OCA], [https://pdbe.org/1d8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d8m RCSB], [https://www.ebi.ac.uk/pdbsum/1d8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d8m 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>
[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.  
[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=1d8m 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=1d8m ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.
Heterocycle-based MMP inhibitors with P2' substituents.,Pikul S, Dunham KM, Almstead NG, De B, Natchus MG, Taiwo YO, Williams LE, Hynd BA, Hsieh LC, Janusz MJ, Gu F, Mieling GE Bioorg Med Chem Lett. 2001 Apr 23;11(8):1009-13. PMID:11327577<ref>PMID:11327577</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1d8m" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Stromelysin 1]]
[[Category: Almstead NG]]
[[Category: Almstead, N G]]
[[Category: De B]]
[[Category: De, B]]
[[Category: Dunham KM]]
[[Category: Dunham, K M]]
[[Category: Gu F]]
[[Category: Gu, F]]
[[Category: Hsieh LC]]
[[Category: Hsieh, L C]]
[[Category: Hynd BA]]
[[Category: Hynd, B A]]
[[Category: Janusz MJ]]
[[Category: Janusz, M J]]
[[Category: Mieling GE]]
[[Category: Mieling, G E]]
[[Category: Natchus MG]]
[[Category: Natchus, M G]]
[[Category: Pikul S]]
[[Category: Pikul, S]]
[[Category: Taiwo YO]]
[[Category: Taiwo, Y O]]
[[Category: Williams LE]]
[[Category: Williams, L E]]
[[Category: Hydrolase]]
[[Category: Inhibited]]
[[Category: Mixed alpha beta structure]]
[[Category: Zinc protease]]

Latest revision as of 09:50, 7 February 2024

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITORCRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR

Structural highlights

1d8m is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.44Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  1. ↑ Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem. 1996 May 31;271(22):13055-60. PMID:8662692
  2. ↑ Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002 Dec 12;347(24):1916-23. PMID:12477941 doi:10.1056/NEJMoa021445

1d8m, resolution 2.44Å

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