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1d8f

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Revision as of 07:22, 10 October 2019

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A PIPERAZINE BASED INHIBITOR.

Structural highlights

1d8f 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
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

A new generation of cyclic matrix metalloproteinase (MMP) inhibitors derived from dl-piperazinecarboxylic acid has been described. The design involves: incorporation of hydroxamic acid as the bidentate chelating agent for catalytic Zn(2+), placement of a sulfonamide group at the 1N-position of the piperazine ring to fill the S1' pocket of the enzyme, and finally attachment of diverse functional groups at the 4N-position to optimize potency and peroral absorption. A unique combination of all three elements produced inhibitor 20 with high affinity for MMPs 1, 3, 9, and 13 (24, 18, 1.9, and 1.3 nM, respectively). X-ray crystallography data obtained for MMP-3 cocrystallized with 20 gave detailed information on key binding interactions defining an overall scaffold geometry for piperazine-based MMP inhibitors.

Design and synthesis of piperazine-based matrix metalloproteinase inhibitors.,Cheng M, De B, Pikul S, Almstead NG, Natchus MG, Anastasio MV, McPhail SJ, Snider CE, Taiwo YO, Chen L, Dunaway CM, Gu F, Dowty ME, Mieling GE, Janusz MJ, Wang-Weigand S J Med Chem. 2000 Feb 10;43(3):369-80. PMID:10669564^[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
↑ Cheng M, De B, Pikul S, Almstead NG, Natchus MG, Anastasio MV, McPhail SJ, Snider CE, Taiwo YO, Chen L, Dunaway CM, Gu F, Dowty ME, Mieling GE, Janusz MJ, Wang-Weigand S. Design and synthesis of piperazine-based matrix metalloproteinase inhibitors. J Med Chem. 2000 Feb 10;43(3):369-80. PMID:10669564

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/1d8f"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A PIPERAZINE BASED INHIBITOR.==
-<StructureSection load='1d8f' size='340' side='right' caption='[[1d8f]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='1d8f' size='340' side='right'caption='[[1d8f]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1d8f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D8F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1D8F FirstGlance]. <br>
@@ Line 32: / Line 32: @@
 </div>
 <div class="pdbe-citations 1d8f" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Matrix metalloproteinase|Matrix metalloproteinase]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Stromelysin 1]]
 [[Category: Almstead, N G]]

1d8f

From Proteopedia

Revision as of 07:22, 10 October 2019

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A PIPERAZINE BASED INHIBITOR.

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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