5BOT

X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate

5BOT の概要

• エントリーDOI: 10.2210/pdb5bot/pdb
• 関連するPDBエントリー: 5BOY 5BPA
• 分子名称: Collagenase 3, ethyl 5-carbamoyl-1H-indole-2-carboxylate, ZINC ION, ... (5 entities in total)
• 機能のキーワード: ridgefield, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 39437.34

構造登録者

Farrow, N.A.,Padyana, A.K. (登録日: 2015-05-27, 公開日: 2015-06-17, 最終更新日: 2024-03-06)

主引用文献

Taylor, S.J.,Abeywardane, A.,Liang, S.,Muegge, I.,Padyana, A.K.,Xiong, Z.,Hill-Drzewi, M.,Farmer, B.,Li, X.,Collins, B.,Li, J.X.,Heim-Riether, A.,Proudfoot, J.,Zhang, Q.,Goldberg, D.,Zuvela-Jelaska, L.,Zaher, H.,Li, J.,Farrow, N.A.
Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13.
J. Med. Chem., 54:8174-8187, 2011

PubMed Abstract: Matrix metalloproteases (MMPs) play an important role in cartilage homeostasis under both normal and inflamed disease states and, thus, have become attractive targets for the treatment of arthritic diseases. Herein, we describe the identification of a potent, selective MMP-13 inhibitor, developed using fragment-based structure-guided lead identification and optimization techniques. Virtual screening methods identified a novel, indole-based MMP-13 inhibitor that bound into the S1' pocket of the protein exhibiting a novel interaction pattern hitherto not observed in MMP-13 inhibitors. X-ray crystallographic structures were used to guide the elaboration of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over nine other MMP isoforms tested.

PubMed: 22017539
DOI: 10.1021/jm201129m

実験手法

X-RAY DIFFRACTION (1.85 Å)