2ovx: Difference between revisions
New page: left|200px<br /> <applet load="2ovx" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ovx, resolution 2.00Å" /> '''MMP-9 active site m... |
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'''MMP-9 active site mutant with barbiturate inhibitor'''<br /> | '''MMP-9 active site mutant with barbiturate inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2OVX 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 ZN, CA, CL and 4MR 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] Full crystallographic information is available from [http:// | 2OVX 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=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=4MR:'>4MR</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OVX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: s1-prime pocket]] | [[Category: s1-prime pocket]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:07:34 2008'' | ||
Revision as of 15:07, 23 January 2008
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MMP-9 active site mutant with barbiturate inhibitor
OverviewOverview
Human matrix metalloproteinase 9 (MMP-9), also called gelatinase B, is, particularly involved in inflammatory processes, bone remodelling and, wound healing, but is also implicated in pathological processes such as, rheumatoid arthritis, atherosclerosis, tumour growth, and metastasis. We, have prepared the inactive E402Q mutant of the truncated catalytic domain, of human MMP-9 and co-crystallized it with active site-directed synthetic, inhibitors of different binding types. Here, we present the X-ray, structures of five MMP-9 complexes with gelatinase-specific, tight binding, inhibitors: a phosphinic acid (AM-409), a pyrimidine-2,4,6-trione, (RO-206-0222), two carboxylate (An-1 and MJ-24), and a trifluoromethyl, hydroxamic acid inhibitor (MS-560). These compounds bind by making a, compromise between optimal coordination of the catalytic zinc, favourable, hydrogen bond formation in the active-site cleft, and accommodation of, their large hydrophobic P1' groups in the slightly flexible S1' cavity, which exhibits distinct rotational conformations of the Pro421 carbonyl, group in each complex. In all these structures, the side-chain of Arg424, located at the bottom of the S1' cavity is not defined in the electron, density beyond C(gamma), indicating its mobility. However, we suggest that, the mobile Arg424 side-chain partially blocks the S1' cavity, which might, explain the weaker binding of most inhibitors with a long P1' side-chain, for MMP-9 compared with the closely related MMP-2 (gelatinase A), which, exhibits a short threonine side-chain at the equivalent position. These, novel structural details should facilitate the design of more selective, MMP-9 inhibitors.
About this StructureAbout this Structure
2OVX 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 Full crystallographic information is available from OCA.
ReferenceReference
Crystal Structures of MMP-9 Complexes with Five Inhibitors: Contribution of the Flexible Arg424 Side-chain to Selectivity., Tochowicz A, Maskos K, Huber R, Oltenfreiter R, Dive V, Yiotakis A, Zanda M, Bode W, Goettig P, J Mol Biol. 2007 Aug 24;371(4):989-1006. Epub 2007 May 31. PMID:17599356
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