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[[Image:1ums.jpg|left|200px]]


{{Structure
==STROMELYSIN-1 CATALYTIC DOMAIN WITH HYDROPHOBIC INHIBITOR BOUND, PH 7.0, 32OC, 20 MM CACL2, 15% ACETONITRILE; NMR ENSEMBLE OF 20 STRUCTURES==
|PDB= 1ums |SIZE=350|CAPTION= <scene name='initialview01'>1ums</scene>
<StructureSection load='1ums' size='340' side='right'caption='[[1ums]]' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=MOP:4-METHYLPENTANAL'>MOP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
<table><tr><td colspan='2'>[[1ums]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UMS FirstGlance]. <br>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
|GENE= HUMAN STROMELYSIN-1 CATALYTIC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0DS:N-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-L-LEUCYL-L-PHENYLALANINAMIDE'>0DS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ums FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ums OCA], [https://pdbe.org/1ums PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ums RCSB], [https://www.ebi.ac.uk/pdbsum/1ums PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ums ProSAT]</span></td></tr>
|RELATEDENTRY=[[1umt|1UMT]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ums FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ums OCA], [http://www.ebi.ac.uk/pdbsum/1ums PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ums RCSB]</span>
== 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>
== 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/um/1ums_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1ums ConSurf].
<div style="clear:both"></div>


'''STROMELYSIN-1 CATALYTIC DOMAIN WITH HYDROPHOBIC INHIBITOR BOUND, PH 7.0, 32OC, 20 MM CACL2, 15% ACETONITRILE; NMR ENSEMBLE OF 20 STRUCTURES'''
==See Also==
 
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 
== References ==
==Overview==
<references/>
Stromelysin, a representative matrix metalloproteinase and target of drug development efforts, plays a prominent role in the pathological proteolysis associated with arthritis and secondarily in that of cancer metastasis and invasion. To provide a structural template to aid the development of therapeutic inhibitors, we have determined a medium-resolution structure of a 20-kDa complex of human stromelysin's catalytic domain with a hydrophobic peptidic inhibitor using multinuclear, multidimensional NMR spectroscopy. This domain of this zinc hydrolase contains a mixed beta-sheet comprising one antiparallel strand and four parallel strands, three helices, and a methionine-containing turn near the catalytic center. The ensemble of 20 structures was calculated using, on average, 8 interresidue NOE restraints per residue for the 166-residue protein fragment complexed with a 4-residue substrate analogue. The mean RMS deviation (RMSD) to the average structure for backbone heavy atoms is 0.91 A and for all heavy atoms is 1.42 A. The structure has good stereochemical properties, including its backbone torsion angles. The beta-sheet and alpha-helices of the catalytic domains of human stromelysin (NMR model) and human fibroblast collagenase (X-ray crystallographic model of Lovejoy B et al., 1994b, Biochemistry 33:8207-8217) superimpose well, having a pairwise RMSD for backbone heavy atoms of 2.28 A when three loop segments are disregarded. The hydroxamate-substituted inhibitor binds across the hydrophobic active site of stromelysin in an extended conformation. The first hydrophobic side chain is deeply buried in the principal S'1 subsite, the second hydrophobic side chain is located on the opposite side of the inhibitor backbone in the hydrophobic S'2 surface subsite, and a third hydrophobic side chain (P'3) lies at the surface.
__TOC__
 
</StructureSection>
==About this Structure==
1UMS is a [[Single protein]] structure of 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=1UMS OCA].
 
==Reference==
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor., Van Doren SR, Kurochkin AV, Hu W, Ye QZ, Johnson LL, Hupe DJ, Zuiderweg ER, Protein Sci. 1995 Dec;4(12):2487-98. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8580839 8580839]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Stromelysin 1]]
[[Category: Hu W]]
[[Category: Doren, S R.Van.]]
[[Category: Kurochkin AV]]
[[Category: Hu, W.]]
[[Category: Van Doren SR]]
[[Category: Kurochkin, A V.]]
[[Category: Zuiderweg ERP]]
[[Category: Zuiderweg, E R.P.]]
[[Category: matrix metalloproteinase]]
[[Category: metzincin]]
[[Category: zinc hydrolase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:12:27 2008''

Latest revision as of 09:35, 1 May 2024

STROMELYSIN-1 CATALYTIC DOMAIN WITH HYDROPHOBIC INHIBITOR BOUND, PH 7.0, 32OC, 20 MM CACL2, 15% ACETONITRILE; NMR ENSEMBLE OF 20 STRUCTURESSTROMELYSIN-1 CATALYTIC DOMAIN WITH HYDROPHOBIC INHIBITOR BOUND, PH 7.0, 32OC, 20 MM CACL2, 15% ACETONITRILE; NMR ENSEMBLE OF 20 STRUCTURES

Structural highlights

1ums is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
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
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