1d5j
From Proteopedia
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CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.
Contents |
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.
Disease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this Structure
1D5J is a Single protein structure of sequence from [1] with ZN, CA and MM3 as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 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 Mon Nov 12 16:29:13 2007
Categories: Single protein | Stromelysin 1 | Almstead, N.G. | Bradley, R.S. | De, B. | Natchus, M.G. | Pikul, S. | CA | MM3 | ZN | Inhibited | Mixed alpha beta structure | Zinc protease
