8HFK

Crystal Structure of CbAR mutant (H162F) in complex with NADP+ and halogenated aryl ketone

8HFK の概要

• エントリーDOI: 10.2210/pdb8hfk/pdb
• 分子名称: Versicolorin reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-bromanyl-1-(4-bromanyl-2-oxidanyl-phenyl)ethanone, ... (4 entities in total)
• 機能のキーワード: anthrol reductase, chiral alcohol, emodin, oxidoreductase
• 由来する生物種: Cercospora sp. JNU001
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124649.14

構造登録者

Hou, X.D.,Yin, D.J.,Rao, Y.J. (登録日: 2022-11-10, 公開日: 2023-06-07, 最終更新日: 2023-11-08)

主引用文献

Hou, X.,Xu, H.,Yuan, Z.,Deng, Z.,Fu, K.,Gao, Y.,Liu, C.,Zhang, Y.,Rao, Y.
Structural analysis of an anthrol reductase inspires enantioselective synthesis of enantiopure hydroxycycloketones and beta-halohydrins.
Nat Commun, 14:353-353, 2023

PubMed Abstract: Asymmetric reduction of prochiral ketones, particularly, reductive desymmetrization of 2,2-disubstituted prochiral 1,3-cyclodiketones to produce enantiopure chiral alcohols is challenging. Herein, an anthrol reductase CbAR with the ability to accommodate diverse bulky substrates, like emodin, for asymmetric reduction is identified. We firstly solve crystal structures of CbAR and CbAR-Emodin complex. It reveals that Tyr210 is critical for emodin recognition and binding, as it forms a hydrogen-bond interaction with His162 and π-π stacking interactions with emodin. This ensures the correct orientation for the stereoselectivity. Then, through structure-guided engineering, variant CbAR-H162F can convert various 2,2-disubstituted 1,3-cyclodiketones and α-haloacetophenones to optically pure (2S, 3S)-ketols and (R)-β-halohydrins, respectively. More importantly, their stereoselectivity mechanisms are also well explained by the respective crystal structures of CbAR-H162F-substrate complex. Therefore, this study demonstrates that an in-depth understanding of catalytic mechanism is valuable for exploiting the promiscuity of anthrol reductases to prepare diverse enantiopure chiral alcohols.

PubMed: 36681664
DOI: 10.1038/s41467-023-36064-4

実験手法

X-RAY DIFFRACTION (2.9 Å)