3LT5

X-ray Crystallographic structure of a Pseudomonas Aeruginosa Azoreductase in complex with balsalazide

3LT5 の概要

• エントリーDOI: 10.2210/pdb3lt5/pdb
• 関連するPDBエントリー: 2V9C 3KEG
• 分子名称: FMN-dependent NADH-azoreductase 1, FLAVIN MONONUCLEOTIDE, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: azoreductase, balsalazide, hydrazo, inflammatory bowel disease, p. aeruginosa, flavoprotein, fmn, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48057.75

構造登録者

Ryan, A.,Laurieri, N.,Westwood, I.,Wang, C.-J.,Lowe, E.,Sim, E. (登録日: 2010-02-15, 公開日: 2010-05-12, 最終更新日: 2023-11-01)

主引用文献

Ryan, A.,Laurieri, N.,Westwood, I.,Wang, C.-J.,Lowe, E.,Sim, E.
A Novel Mechanism for Azoreduction
J.Mol.Biol., 400:24-37, 2010

PubMed Abstract: Azoreductases are important due to their ability to activate anti-inflammatory azo pro-drugs and to detoxify azo dyes. Three genes encoding azoreductases have been identified in Pseudomonas aeruginosa. We describe here a comparison of the three enzymes. The pure recombinant proteins each have a distinct substrate specificity profile against a range of azo substrates. Using the structure of P. aeruginosa azoreductase (paAzoR) 1 and the homology models of paAzoR2 and paAzoR3, we have identified residues important for substrate specificity. We have defined a novel flavin mononucleotide binding cradle, which is a recurrent motif in many flavodoxin-like proteins. A novel structure of paAzoR1 with the azo pro-drug balsalazide bound within the active site was determined by X-ray crystallography and demonstrates that the substrate is present in a hydrazone tautomer conformation. We propose that the structure with balsalazide bound represents an enzyme intermediate and, together with the flavin mononucleotide binding cradle, we propose a novel catalytic mechanism.

PubMed: 20417637
DOI: 10.1016/j.jmb.2010.04.023

実験手法

X-RAY DIFFRACTION (2.3 Å)