1d8m
From Proteopedia
(New page: 200px<br /> <applet load="1d8m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d8m, resolution 2.44Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1d8m.gif|left|200px]]<br /> | + | [[Image:1d8m.gif|left|200px]]<br /><applet load="1d8m" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1d8m" size=" | + | |
caption="1d8m, resolution 2.44Å" /> | caption="1d8m, resolution 2.44Å" /> | ||
'''CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Potent and selective inhibition of matrix metalloproteinases was | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1D8M 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 and BBH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1D8M 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> and <scene name='pdbligand=BBH:'>BBH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D8M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Stromelysin 1]] | [[Category: Stromelysin 1]] | ||
| - | [[Category: Almstead, N | + | [[Category: Almstead, N G.]] |
[[Category: De, B.]] | [[Category: De, B.]] | ||
| - | [[Category: Dunham, K | + | [[Category: Dunham, K M.]] |
[[Category: Gu, F.]] | [[Category: Gu, F.]] | ||
| - | [[Category: Hsieh, L | + | [[Category: Hsieh, L C.]] |
| - | [[Category: Hynd, B | + | [[Category: Hynd, B A.]] |
| - | [[Category: Janusz, M | + | [[Category: Janusz, M J.]] |
| - | [[Category: Mieling, G | + | [[Category: Mieling, G E.]] |
| - | [[Category: Natchus, M | + | [[Category: Natchus, M G.]] |
[[Category: Pikul, S.]] | [[Category: Pikul, S.]] | ||
| - | [[Category: Taiwo, Y | + | [[Category: Taiwo, Y O.]] |
| - | [[Category: Williams, L | + | [[Category: Williams, L E.]] |
[[Category: BBH]] | [[Category: BBH]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: zinc protease]] | [[Category: zinc protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:08 2008'' |
Revision as of 10:14, 21 February 2008
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CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this Structure
1D8M is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 Full crystallographic information is available from 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:11327577
Page seeded by OCA on Thu Feb 21 12:14:08 2008
Categories: Homo sapiens | Single protein | Stromelysin 1 | Almstead, N G. | De, B. | Dunham, K M. | Gu, F. | Hsieh, L C. | Hynd, B A. | Janusz, M J. | Mieling, G E. | Natchus, M G. | Pikul, S. | Taiwo, Y O. | Williams, L E. | BBH | CA | ZN | Inhibited | Mixed alpha beta structure | Zinc protease
