1gkc: Difference between revisions
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[[Image:1gkc.gif|left|200px]]<br /><applet load="1gkc" size=" | [[Image:1gkc.gif|left|200px]]<br /><applet load="1gkc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1gkc, resolution 2.30Å" /> | caption="1gkc, resolution 2.30Å" /> | ||
'''MMP9-INHIBITOR COMPLEX'''<br /> | '''MMP9-INHIBITOR COMPLEX'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1GKC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, ZN and BUM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] Known structural/functional Site: <scene name='pdbsite=BUA:Zn Binding Site For Chain B'>BUA</scene>. Full crystallographic information is available from [http:// | 1GKC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=BUM:'>BUM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] Known structural/functional Site: <scene name='pdbsite=BUA:Zn+Binding+Site+For+Chain+B'>BUA</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GKC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: matrix metalloprotease]] | [[Category: matrix metalloprotease]] | ||
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Revision as of 10:40, 3 February 2008
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MMP9-INHIBITOR COMPLEX
OverviewOverview
Matrix metalloproteinases (MMPs) and their inhibitors are important in, connective tissue re-modelling in diseases of the cardiovascular system, such as atherosclerosis. Various members of the MMP family have been shown, to be expressed in atherosclerotic lesions, but MMP9 is consistently seen, in inflammatory atherosclerotic lesions. MMP9 over-expression is, implicated in the vascular re-modelling events preceding plaque rupture, (the most common cause of acute myocardial infarction). Reduced MMP9, activity, either by genetic manipulation or through pharmacological, intervention, has an impact on ventricular re-modelling following, infarction. MMP9 activity may therefore represent a key mechanism in the, pathogenesis of heart failure. We have determined the crystal structure, at 2.3 A resolution, of the catalytic domain of human MMP9 bound to a, peptidic reverse hydroxamate inhibitor as well as the complex of the same, inhibitor bound to an active-site mutant (E402Q) at 2.1 A resolution. MMP9, adopts the typical MMP fold. The catalytic centre is composed of the, active-site zinc ion, co-ordinated by three histidine residues (401, 405, and 411) and the essential glutamic acid residue (402). The main, differences between the catalytic domains of various MMPs occur in the S1', subsite or selectivity pocket. The S1' specificity site in MMP9 is perhaps, best described as a tunnel leading toward solvent, as in MMP2 and MMP13, as opposed to the smaller pocket found in fibroblast collagenase and, matrilysin. The present structure enables us to aid the design of potent, and specific inhibitors for this important cardiovascular disease target.
About this StructureAbout this Structure
1GKC is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Gelatinase B, with EC number 3.4.24.35 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor., Rowsell S, Hawtin P, Minshull CA, Jepson H, Brockbank SM, Barratt DG, Slater AM, McPheat WL, Waterson D, Henney AM, Pauptit RA, J Mol Biol. 2002 May 24;319(1):173-81. PMID:12051944
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