1d5j
From Proteopedia
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|PDB= 1d5j |SIZE=350|CAPTION= <scene name='initialview01'>1d5j</scene>, resolution 2.6Å | |PDB= 1d5j |SIZE=350|CAPTION= <scene name='initialview01'>1d5j</scene>, resolution 2.6Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MM3:N-HYDROXY-4-[(4-METHOXYLPHENYL)SULFONYL]-2,2-DIMETHYL-HEXAHYDRO-1,4-THIAZEPINE-3(S)-CARBOXAMIDE'>MM3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1cqr|1CQR]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5j OCA], [http://www.ebi.ac.uk/pdbsum/1d5j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d5j RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a. | The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=185250 185250]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Natchus, M G.]] | [[Category: Natchus, M G.]] | ||
[[Category: Pikul, S.]] | [[Category: Pikul, S.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: MM3]] | ||
| - | [[Category: ZN]] | ||
[[Category: inhibited]] | [[Category: inhibited]] | ||
[[Category: mixed alpha beta structure]] | [[Category: mixed alpha beta structure]] | ||
[[Category: zinc protease]] | [[Category: zinc protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:35:06 2008'' |
Revision as of 16:35, 30 March 2008
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| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Stromelysin 1, with EC number 3.4.24.17 | ||||||
| Related: | 1CQR
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.
Overview
The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.
About this Structure
1D5J is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors., Almstead NG, Bradley RS, Pikul S, De B, Natchus MG, Taiwo YO, Gu F, Williams LE, Hynd BA, Janusz MJ, Dunaway CM, Mieling GE, J Med Chem. 1999 Nov 4;42(22):4547-62. PMID:10579818
Page seeded by OCA on Sun Mar 30 19:35:06 2008
