4BII

How nature bridges the gap: Crystallographic elucidation of pyridomycin binding to InhA

4BII の概要

• エントリーDOI: 10.2210/pdb4bii/pdb
• 関連するPDBエントリー: 4BGE
• 分子名称: ENOYL-[ACYL-CARRIER-PROTEIN] REDUCTASE [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, Pyridomycin, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, acp enoyl reductase
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117831.09

構造登録者

Read, J.A.,Gingell, H. (登録日: 2013-04-10, 公開日: 2013-12-04, 最終更新日: 2024-05-08)

主引用文献

Hartkoorn, R.,Pojer, F.,Read, J.A.,Gingell, H.,Neres, J.,Horlacher, O.,Altmann, K.H.,Cole, S.
Pyridomycin Bridges the Nadh and Substrate Binding Pockets of the Enoyl Reductase Inha
Nat.Chem.Biol., 10:96-, 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 (1.95 Å)