4BGE

Crystal structure of InhA(S94A) mutant in complex with pyridomycin

4BGE の概要

• エントリーDOI: 10.2210/pdb4bge/pdb
• 関連するPDBエントリー: 4BGI
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH], Pyridomycin (3 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 174476.08

構造登録者

Pojer, F.,Hartkoorn, R.C.,Cole, S.T. (登録日: 2013-03-26, 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 (2.25 Å)