1g4k

From Proteopedia

(Difference between revisions)

Revision as of 20:31, 22 December 2014

X-ray Structure of a Novel Matrix Metalloproteinase Inhibitor Complexed to Stromelysin

Structural highlights

1g4k is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Activity:	Stromelysin 1, with EC number 3.4.24.17
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 PubMed

A new class of matrix metalloproteinase (MMP) inhibitors has been identified by screening a collection of compounds against stromelysin. The inhibitors, 2,4,6-pyrimidine triones, have proven to be potent inhibitors of gelatinases A and B. An X-ray crystal structure of one representative compound bound to the catalytic domain of stromelysin shows that the compounds bind at the active site and ligand the active-site zinc. The pyrimidine triones mimic substrates in forming hydrogen bonds to key residues in the active site, and provide opportunities for placing appropriately chosen groups into the S1' specificity pocket of MMPS: A number of compounds have been synthesized and assayed against stromelysin, and the variations in potency are explained in terms of the binding mode revealed in the X-ray crystal structure.

X-ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin.,Dunten P, Kammlott U, Crowther R, Levin W, Foley LH, Wang P, Palermo R Protein Sci. 2001 May;10(5):923-6. PMID:11316871^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ Dunten P, Kammlott U, Crowther R, Levin W, Foley LH, Wang P, Palermo R. X-ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin. Protein Sci. 2001 May;10(5):923-6. PMID:11316871

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1g4k"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1g4k]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G4K FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HQQ:5-METHYL-5-(4-PHENOXY-PHENYL)-PYRIMIDINE-2,4,6-TRIONE'>HQQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HQQ:5-METHYL-5-(4-PHENOXY-PHENYL)-PYRIMIDINE-2,4,6-TRIONE'>HQQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1g4k RCSB], [http://www.ebi.ac.uk/pdbsum/1g4k PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1g4k RCSB], [http://www.ebi.ac.uk/pdbsum/1g4k PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN]] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM:[http://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>
@@ Line 38: / Line 38: @@
 [[Category: Homo sapiens]]
 [[Category: Stromelysin 1]]
-[[Category: Crowther, R.]]
+[[Category: Crowther, R]]
-[[Category: Dunten, P.]]
+[[Category: Dunten, P]]
-[[Category: Foley, L H.]]
+[[Category: Foley, L H]]
-[[Category: Kammlott, U.]]
+[[Category: Kammlott, U]]
-[[Category: Levin, W.]]
+[[Category: Levin, W]]
-[[Category: Palermo, R.]]
+[[Category: Palermo, R]]
-[[Category: Wang, P.]]
+[[Category: Wang, P]]
 [[Category: Hydrolase]]
 [[Category: Mmp]]
 [[Category: Stomelysin]]
 [[Category: Zinc ligand]]

1g4k

From Proteopedia

Revision as of 20:31, 22 December 2014

X-ray Structure of a Novel Matrix Metalloproteinase Inhibitor Complexed to Stromelysin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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