7A3W

Structure of Imine Reductase from Pseudomonas sp.

7A3W の概要

• エントリーDOI: 10.2210/pdb7a3w/pdb
• 分子名称: NAD(P)-dependent oxidoreductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: imine, enimine, nadph, oxidoreductase
• 由来する生物種: Pseudomonas putida
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63917.70

構造登録者

Cuetos, A.,Thorpe, T.,Turner, N.J.,Grogan, G. (登録日: 2020-08-18, 公開日: 2021-08-25, 最終更新日: 2024-02-07)

主引用文献

Thorpe, T.W.,Marshall, J.R.,Harawa, V.,Ruscoe, R.E.,Cuetos, A.,Finnigan, J.D.,Angelastro, A.,Heath, R.S.,Parmeggiani, F.,Charnock, S.J.,Howard, R.M.,Kumar, R.,Daniels, D.S.B.,Grogan, G.,Turner, N.J.
Multifunctional biocatalyst for conjugate reduction and reductive amination.
Nature, 604:86-91, 2022

PubMed Abstract: Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals, yet their preparation often relies on low-efficiency multi-step synthesis. These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein we characterize a multifunctional biocatalyst for amine synthesis, which operates using a mechanism that is, to our knowledge, previously unreported. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers bearing up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED, which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.

PubMed: 35388195
DOI: 10.1038/s41586-022-04458-x

実験手法

X-RAY DIFFRACTION (1.59 Å)