4I1W

2.00 Angstroms X-ray crystal structure of NAD- bound 2-aminomuconate 6-semialdehyde dehydrogenase from Pseudomonas fluorescens

4I1W の概要

• エントリーDOI: 10.2210/pdb4i1w/pdb
• 関連するPDBエントリー: 4I25 4I26 4I2R
• 分子名称: 2-aminomuconate 6-semialdehyde dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: aldehyde dehydrogenase, dehydrogenase, nad, oxidoreductase
• 由来する生物種: Pseudomonas fluorescens
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 218740.61

構造登録者

Huo, L.,Davis, I.,Chen, L.,Liu, A. (登録日: 2012-11-21, 公開日: 2014-05-21, 最終更新日: 2023-09-20)

主引用文献

Huo, L.,Davis, I.,Liu, F.,Andi, B.,Esaki, S.,Iwaki, H.,Hasegawa, Y.,Orville, A.M.,Liu, A.
Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action.
Nat Commun, 6:5935-5935, 2015

PubMed Abstract: Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for 'disarming' the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl intermediate and an NAD(+)-bound complex from an active site mutant. These covalent intermediates are characterized by single-crystal and solution-state electronic absorption spectroscopy. The crystal structures reveal that the substrate undergoes an E/Z isomerization at the enzyme active site before an sp(3)-to-sp(2) transition during enzyme-mediated oxidation.

PubMed: 25565451
DOI: 10.1038/ncomms6935

実験手法

X-RAY DIFFRACTION (1.992 Å)