2014年2月7日
Structural basis of stereospecific reduction by quinuclidinone reductase
AMB Express
- 巻
- 4
- 号
- 1
- 開始ページ
- 6
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1186/2191-0855-4-6
- 出版者・発行元
- BIOMED CENTRAL LTD
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 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.
- リンク情報
- ID情報
-
- DOI : 10.1186/2191-0855-4-6
- ISSN : 2191-0855
- PubMed ID : 24507746
- Web of Science ID : WOS:000358051800001