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Crystal structure of NADPH-Dependent 3-Quinuclidinone Reductase from Rhodotorula RubraCrystal structure of NADPH-Dependent 3-Quinuclidinone Reductase from Rhodotorula Rubra
Structural highlights
FunctionPublication Abstract from PubMedChiral molecule (R)-3-quinuclidinol, a valuable compound for the production of various pharmaceuticals, is efficiently synthesized from 3-quinuclidinone by using NADPH-dependent 3-quinuclidinone reductase (RrQR) from Rhodotorula rubra. Here, we report the crystal structure of RrQR and the structure-based mutational analysis. The enzyme forms a tetramer, in which the core of each protomer exhibits the alpha/beta Rossmann fold and contains one molecule of NADPH, whereas the characteristic substructures of a small lobe and a variable loop are localized around the substrate-binding site. Modeling and mutation analyses of the catalytic site indicated that the hydrophobicity of two residues, I167 and F212, determines the substrate-binding orientation as well as the substrate-binding affinity. Our results revealed that the characteristic substrate-binding pocket composed of hydrophobic amino acid residues ensures substrate docking for the stereospecific reaction of RrQR in spite of its loose interaction with the substrate. Structural basis of stereospecific reduction by quinuclidinone reductase.,Takeshita D, Kataoka M, Miyakawa T, Miyazono K, Kumashiro S, Nagai T, Urano N, Uzura A, Nagata K, Shimizu S, Tanokura M AMB Express. 2014 Feb 7;4(1):6. doi: 10.1186/2191-0855-4-6. PMID:24507746[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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