8hfj

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

spinqualitylabelsall models 8hfj, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hfj is a 4 chain structure with sequence from Cercospora sojina. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.75Å Ligands: L7Z, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2G5I2X5_CERBT Publication Abstract from PubMed 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 pi-pi 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 alpha-haloacetophenones to optically pure (2S, 3S)-ketols and (R)-beta-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. Structural analysis of an anthrol reductase inspires enantioselective synthesis of enantiopure hydroxycycloketones and beta-halohydrins.,Hou X, Xu H, Yuan Z, Deng Z, Fu K, Gao Y, Liu C, Zhang Y, Rao Y Nat Commun. 2023 Jan 21;14(1):353. doi: 10.1038/s41467-023-36064-4. PMID:36681664 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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