7XEE

Crystal Structure of the Y53F/N55A mutant of LEH complexed with 2-(3-phenyloxetan-3-yl)ethanamine

7XEE の概要

• エントリーDOI: 10.2210/pdb7xee/pdb
• 分子名称: Limonene-1,2-epoxide hydrolase, 2-(3-phenyloxetan-3-yl)ethanamine, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: limonene-1, 2-epoxide hydrolase, mutant, rhodococcus erythropolis, hydrolase
• 由来する生物種: Rhodococcus erythropolis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35156.46

構造登録者

Qu, G.,Li, X.,Sun, Z.T. (登録日: 2022-03-31, 公開日: 2023-01-18, 最終更新日: 2023-11-29)

主引用文献

Li, J.K.,Qu, G.,Li, X.,Tian, Y.,Cui, C.,Zhang, F.G.,Zhang, W.,Ma, J.A.,Reetz, M.T.,Sun, Z.
Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles.
Nat Commun, 13:7813-7813, 2022

PubMed Abstract: Chiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles.

PubMed: 36535947
DOI: 10.1038/s41467-022-35468-y

実験手法

X-RAY DIFFRACTION (1.877 Å)