6XNB
The Crystal Structure of the S154Y Mutant Carbonyl Reductase from Leifsonia xyli Explains Enhanced Activity for 3,5-Bis(trifluoromethyl)acetophenone Reduction
Summary for 6XNB
| Entry DOI | 10.2210/pdb6xnb/pdb |
| Related | 6XMW |
| Descriptor | Short chain alcohol dehydrogenase, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | carbonyl reductase, leifsonia xyli, l. xyli, oxidoreductase |
| Biological source | Leifsonia xyli |
| Total number of polymer chains | 1 |
| Total formula weight | 25137.01 |
| Authors | Dinh, T.,Phillips, R. (deposition date: 2020-07-02, release date: 2020-08-12, Last modification date: 2023-10-18) |
| Primary citation | 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 Cited by 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: 35247363DOI: 10.1016/j.abb.2022.109158 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.16 Å) |
Structure validation
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