7E48

Crystal structure of InhA in complex with 3-nitropropanoic acid inhibitor

7E48 の概要

• エントリーDOI: 10.2210/pdb7e48/pdb
• 関連するPDBエントリー: 6R9W
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 3-NITROPROPANOIC ACID, ... (5 entities in total)
• 機能のキーワード: enoyl-acp reductase, fas-ii enoyl-acp reductase, nadh- dependent 2-trans-enoyl-acp reductase, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117441.22

構造登録者

Songsiriritthigul, C.,Hanwarinroj, C.,Suttipanta, N.,Kamsri, P.,Kittakoop, P.,Pungpo, P. (登録日: 2021-02-10, 公開日: 2021-11-24, 最終更新日: 2023-11-29)

主引用文献

Songsiriritthigul, C.,Hanwarinroj, C.,Pakamwong, B.,Srimanote, P.,Suttipanta, N.,Sureram, S.,Suttisintong, K.,Kamsri, P.,Punkvang, A.,Spencer, J.,Kittakoop, P.,Pungpo, P.
Inhibition of Mycobacterium tuberculosis InhA by 3-nitropropanoic acid.
Proteins, 90:898-904, 2022

PubMed Abstract: 3-Nitropropanoic acid (3NP), a bioactive fungal natural product, was previously demonstrated to inhibit growth of Mycobacterium tuberculosis. Here we demonstrate that 3NP inhibits the 2-trans-enoyl-acyl carrier protein reductase (InhA) from Mycobacterium tuberculosis with an IC value of 71 μM, and present the crystal structure of the ternary InhA-NAD -3NP complex. The complex contains the InhA substrate-binding loop in an ordered, open conformation with Tyr158, a catalytically important residue whose orientation defines different InhA substrate/inhibitor complex conformations, in the "out" position. 3NP occupies a hydrophobic binding site adjacent to the NAD cofactor and close to that utilized by the diphenyl ether triclosan, but binds predominantly via electrostatic and water-mediated hydrogen-bonding interactions with the protein backbone and NAD cofactor. The identified mode of 3NP binding provides opportunities to improve inhibitory activity toward InhA.

PubMed: 34677871
DOI: 10.1002/prot.26268

実験手法

X-RAY DIFFRACTION (2.5 Å)