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1bm6

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Revision as of 18:01, 14 August 2019

SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN STROMELYSIN-1 COMPLEXED TO A POTENT NON-PEPTIDIC INHIBITOR, NMR, 20 STRUCTURES

Structural highlights

1bm6 is a 1 chain structure with sequence from Human. Full experimental 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, 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

The full three-dimensional structure of the catalytic domain of human stromelysin-1 (SCD) complexed to a novel and potent, nonpeptidic inhibitor has been determined by nuclear magnetic resonance spectroscopy (NMR). To accurately mimic assay conditions, the structure was obtained in Tris buffer at pH 6.8 and without the presence of organic solvent. The results showed that the major site of enzyme-inhibitor interaction occurs in the S1' pocket whereas portions of the inhibitor that occupy the shallow S2' and S1 pockets remained primarily solvent exposed. Because this relatively small inhibitor could not deeply penetrate stromelysin's long narrow hydrophobic S1' pocket, the enzyme was found to adopt a dramatic fold in the loop region spanning residues 221-231, allowing occupation of the solvent-accessible S1' channel by the enzyme itself. This remarkable conformational fold at the enzyme binding site resulted in constriction of the S1' loop region about the inhibitor. Examination of the tertiary structure of the stromelysin-inhibitor complex revealed few hydrogen-bonding or hydrophobic interactions between the inhibitor and enzyme that can contribute to overall binding energy; hence the resultant compact structure may in part account for the relatively high potency exhibited by this inhibitor.

Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor.,Li YC, Zhang X, Melton R, Ganu V, Gonnella NC Biochemistry. 1998 Oct 6;37(40):14048-56. PMID:9760240^[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
↑ Li YC, Zhang X, Melton R, Ganu V, Gonnella NC. Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor. Biochemistry. 1998 Oct 6;37(40):14048-56. PMID:9760240 doi:http://dx.doi.org/10.1021/bi981328w

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/1bm6"

@@ Line 1: / Line 1: @@
 ==SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN STROMELYSIN-1 COMPLEXED TO A POTENT NON-PEPTIDIC INHIBITOR, NMR, 20 STRUCTURES==
-<StructureSection load='1bm6' size='340' side='right' caption='[[1bm6]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1bm6' size='340' side='right'caption='[[1bm6]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1bm6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BM6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BM6 FirstGlance]. <br>
@@ Line 16: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/1bm6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/1bm6_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1bm6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Matrix metalloproteinase|Matrix metalloproteinase]]
 == References ==
 <references/>
@@ Line 36: / Line 39: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Stromelysin 1]]
 [[Category: Ganu, V]]

1bm6

From Proteopedia

Revision as of 18:01, 14 August 2019

SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN STROMELYSIN-1 COMPLEXED TO A POTENT NON-PEPTIDIC INHIBITOR, NMR, 20 STRUCTURES

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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