| Structural highlights
1d8m is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 1cqr, 1d5j, 1d7x, 1d8f |
| Activity: | Stromelysin 1, with EC number 3.4.24.17 |
| 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.
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[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
- ↑ Pikul S, Dunham KM, Almstead NG, De B, Natchus MG, Taiwo YO, Williams LE, Hynd BA, Hsieh LC, Janusz MJ, Gu F, Mieling GE. Heterocycle-based MMP inhibitors with P2' substituents. Bioorg Med Chem Lett. 2001 Apr 23;11(8):1009-13. PMID:11327577
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