1D5J
CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.
Summary for 1D5J
| Entry DOI | 10.2210/pdb1d5j/pdb |
| Related | 1CQR |
| Descriptor | STROMELYSIN-1, ZINC ION, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | mixed alpha beta structure, zinc protease, inhibited, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 40084.11 |
| Authors | Almstead, N.G.,Bradley, R.S.,Pikul, S.,De, B.,Natchus, M.G. (deposition date: 1999-10-07, release date: 2000-10-09, Last modification date: 2024-02-07) |
| Primary citation | Almstead, N.G.,Bradley, R.S.,Pikul, S.,De, B.,Natchus, M.G.,Taiwo, Y.O.,Gu, F.,Williams, L.E.,Hynd, B.A.,Janusz, M.J.,Dunaway, C.M.,Mieling, G.E. Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors. J.Med.Chem., 42:4547-4562, 1999 Cited by PubMed Abstract: 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. PubMed: 10579818DOI: 10.1021/jm990330y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
Download full validation report
