8HFJ

Crystal Structure of CbAR mutant (H162F) in complex with NADP+ and a bulky 1,3-cyclodiketone

Summary for 8HFJ

• Entry DOI: 10.2210/pdb8hfj/pdb
• Descriptor: Versicolorin reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-methyl-2-[(4-methylphenyl)methyl]cyclopentane-1,3-dione, ... (4 entities in total)
• Functional Keywords: anthrol reductase, chiral alcohol, emodin, oxidoreductase
• Biological source: Cercospora sp. JNU001
• Total number of polymer chains: 4
• Total formula weight: 123905.93

Authors

Hou, X.D.,Yin, D.J.,Rao, Y.J. (deposition date: 2022-11-10, release date: 2023-06-07, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.75 Å)