3NRC

Crystal Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD+ and triclosan

3NRC の概要

• エントリーDOI: 10.2210/pdb3nrc/pdb
• 分子名称: Enoyl-[acyl-carrier-protein] reductase (NADH), NICOTINAMIDE-ADENINE-DINUCLEOTIDE, TRICLOSAN, ... (4 entities in total)
• 機能のキーワード: rossmann fold, enoyl-acyl carrier protein reductase, nadh binding, oxidoreductase
• 由来する生物種: Francisella tularensis subsp. tularensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61919.06

構造登録者

Mehboob, S.,Santarsiero, B.D.,Truong, K.,Johnson, M.E. (登録日: 2010-06-30, 公開日: 2010-11-10, 最終更新日: 2023-09-06)

主引用文献

Mehboob, S.,Truong, K.,Santarsiero, B.D.,Johnson, M.E.
Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD(+) and triclosan.
Acta Crystallogr.,Sect.F, 66:1436-1440, 2010

PubMed Abstract: Enoyl-acyl carrier protein reductase (FabI) catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antimicrobial drug target in Francisella tularensis. The development of new antibiotic therapies is important both to combat potential drug-resistant bioweapons and to address the broader societal problem of increasing antibiotic resistance among many pathogenic bacteria. The crystal structure of FabI from F. tularensis (FtuFabI) in complex with the inhibitor triclosan and the cofactor NAD(+) has been solved to a resolution of 2.1 Å. Triclosan is known to effectively inhibit FabI from different organisms. Precise characterization of the mode of triclosan binding is required to develop highly specific inhibitors. Comparison of our structure with the previously determined FtuFabI structure (PDB code 2jjy) which is bound to only NAD(+) reveals the conformation of the substrate-binding loop, electron density for which was missing in the earlier structure, and demonstrates a shift in the conformation of the NAD(+) cofactor. This shift in the position of the phosphate groups allows more room in the active site for substrate or inhibitor to bind and be better accommodated. This information will be crucial for virtual screening studies to identify novel scaffolds for development into new active inhibitors.

PubMed: 21045289
DOI: 10.1107/S1744309110039862

実験手法

X-RAY DIFFRACTION (2.101 Å)