6XNB

The Crystal Structure of the S154Y Mutant Carbonyl Reductase from Leifsonia xyli Explains Enhanced Activity for 3,5-Bis(trifluoromethyl)acetophenone Reduction

6XNB の概要

• エントリーDOI: 10.2210/pdb6xnb/pdb
• 関連するPDBエントリー: 6XMW
• 分子名称: Short chain alcohol dehydrogenase, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: carbonyl reductase, leifsonia xyli, l. xyli, oxidoreductase
• 由来する生物種: Leifsonia xyli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25137.01

構造登録者

Dinh, T.,Phillips, R. (登録日: 2020-07-02, 公開日: 2020-08-12, 最終更新日: 2023-10-18)

主引用文献

Li, J.,Dinh, T.,Phillips, R.
The crystal structure of the S154Y mutant carbonyl reductase from Leifsonia xyli explains enhanced activity for 3,5-bis(trifluoromethyl)acetophenone reduction.
Arch.Biochem.Biophys., 720:109158-109158, 2022

PubMed Abstract: Carbonyl reductase from Leifsonia xyli (LXCAR, UniProtKB - T2FLN4) can stereoselectively catalyze the reduction of 3,5-bis(trifluoromethyl)acetophenone (BTAP) to its corresponding alcohol, (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol ((R)-BTPE), which is a valuable chiral intermediate for the synthesis of antiemetic drugs, Aprepitant and Fosaprepitant. Moreover, this protein was found to have a broad spectrum of substrate specificity and can asymmetrically catalyze the reduction of a variety of ketones and keto esters. Even though molecular modelling of this protein was done by Wang et al. (2014), a crystal structure has not yet obtained. In this study, a single mutant, S154Y, which was shown to have higher catalytic activity toward BTAP than that of the wild type, was overexpressed in Escherichia coli BL21 (DE3), purified, and crystallized. The crystal structure of LXCAR-S154Y explains how the mutant enzyme can work with BTAP more efficiently than wild type carbonyl reductase. Furthermore, the structure explains why LXCAR-S154Y can use either NADH or NADPH efficiently as a cofactor, as well as elucidates a proton relay system present in the enzyme.

PubMed: 35247363
DOI: 10.1016/j.abb.2022.109158

実験手法

X-RAY DIFFRACTION (1.16 Å)