Title |
Structural basis of stereospecific reduction by quinuclidinone reductase
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Published in |
AMB Express, February 2014
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DOI | 10.1186/2191-0855-4-6 |
Pubmed ID | |
Authors |
Daijiro Takeshita, Michihiko Kataoka, Takuya Miyakawa, Ken-ichi Miyazono, Shoko Kumashiro, Takahiro Nagai, Nobuyuki Urano, Atsuko Uzura, Koji Nagata, Sakayu Shimizu, Masaru Tanokura |
Abstract |
Chiral 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 α/β 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. |
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