4BGI

Crystal structure of InhA(S94A) mutant in complex with OH-141

4BGI の概要

• エントリーDOI: 10.2210/pdb4bgi/pdb
• 関連するPDBエントリー: 4BGE
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH], 3-hydroxy-N-[(2R,5R,6S,9S,10S,11R)-10-hydroxy-5,11-dimethyl-3,7,12-trioxo-2-(propan-2-yl)-9-(pyridin-3-ylmethyl)-1,4-dioxa-8-azacyclododecan-6-yl]pyridine-2-carboxamide, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, tuberculosis drug
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 183673.82

構造登録者

Pojer, F.,Hartkoorn, R.C.,Cole, S.T. (登録日: 2013-03-27, 公開日: 2013-12-04, 最終更新日: 2023-12-20)

主引用文献

Hartkoorn, R.C.,Pojer, F.,Read, J.A.,Gingell, H.,Neres, J.,Horlacher, O.P.,Altmann, K.H.,Cole, S.T.
Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA.
Nat. Chem. Biol., 10:96-98, 2014

PubMed Abstract: Pyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a-kind binding mode that discloses a new means of InhA inhibition. Proof-of-principle studies show how structure-assisted drug design can improve the activity of new pyridomycin derivatives.

PubMed: 24292073
DOI: 10.1038/nchembio.1405

実験手法

X-RAY DIFFRACTION (2.09 Å)