1g05: Difference between revisions

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[[Image:1g05.gif|left|200px]]


{{Structure
==HETEROCYCLE-BASED MMP INHIBITOR WITH P2'SUBSTITUENTS==
|PDB= 1g05 |SIZE=350|CAPTION= <scene name='initialview01'>1g05</scene>, resolution 2.45&Aring;
<StructureSection load='1g05' size='340' side='right'caption='[[1g05]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=BBH:1-BENZYL-3-(4-METHOXY-BENZENESULFONYL)-6-OXO-HEXAHYDRO-PYRIMIDINE-4-CARBOXYLIC+ACID+HYDROXYAMIDE'>BBH</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
<table><tr><td colspan='2'>[[1g05]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G05 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">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBH:1-BENZYL-3-(4-METHOXY-BENZENESULFONYL)-6-OXO-HEXAHYDRO-PYRIMIDINE-4-CARBOXYLIC+ACID+HYDROXYAMIDE'>BBH</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=1g05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g05 OCA], [https://pdbe.org/1g05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g05 RCSB], [https://www.ebi.ac.uk/pdbsum/1g05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g05 ProSAT]</span></td></tr>
|RELATEDENTRY=[[1cqr|1CQR]], [[1d5j|1D5J]], [[1d7x|1D7X]], [[1d8f|1D8F]], [[1d8m|1D8M]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g05 OCA], [http://www.ebi.ac.uk/pdbsum/1g05 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1g05 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/g0/1g05_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=1g05 ConSurf].
<div style="clear:both"></div>


'''HETEROCYCLE-BASED MMP INHIBITOR WITH P2'SUBSTITUENTS'''
==See Also==
 
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 
== References ==
==Overview==
<references/>
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.
__TOC__
 
</StructureSection>
==About this Structure==
1G05 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=1G05 OCA].
 
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/11327577 11327577]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Stromelysin 1]]
[[Category: Almstead NG]]
[[Category: Almstead, N G.]]
[[Category: De B]]
[[Category: De, B.]]
[[Category: Dunham KM]]
[[Category: Dunham, K M.]]
[[Category: Hsieh LC]]
[[Category: Hsieh, L C.]]
[[Category: Hynd BA]]
[[Category: Hynd, B A.]]
[[Category: Janusz MJ]]
[[Category: Janusz, M J.]]
[[Category: Natchus MG]]
[[Category: Natchus, M G.]]
[[Category: Pikul S]]
[[Category: Pikul, S.]]
[[Category: Taiwo YO]]
[[Category: Taiwo, Y O.]]
[[Category: Williams LE]]
[[Category: Williams, L E.]]
[[Category: inhibited]]
[[Category: mixed alpha beta structure]]
[[Category: zinc protease]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:33:43 2008''

Latest revision as of 10:21, 7 February 2024

HETEROCYCLE-BASED MMP INHIBITOR WITH P2'SUBSTITUENTSHETEROCYCLE-BASED MMP INHIBITOR WITH P2'SUBSTITUENTS

Structural highlights

1g05 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.45Å
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

1g05, resolution 2.45Å

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