1D5J

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.

1D5J の概要

• エントリーDOI: 10.2210/pdb1d5j/pdb
• 関連するPDBエントリー: 1CQR
• 分子名称: STROMELYSIN-1, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: mixed alpha beta structure, zinc protease, inhibited, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40084.11

構造登録者

Almstead, N.G.,Bradley, R.S.,Pikul, S.,De, B.,Natchus, M.G. (登録日: 1999-10-07, 公開日: 2000-10-09, 最終更新日: 2024-02-07)

主引用文献

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

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: 10579818
DOI: 10.1021/jm990330y

実験手法

X-RAY DIFFRACTION (2.6 Å)