2011年1月
Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the role of His269 in coenzyme binding by site-directed mutagenesis
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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- 巻
- 21
- 号
- 2
- 開始ページ
- 801
- 終了ページ
- 804
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/j.bmcl.2010.11.086
- 出版者・発行元
- PERGAMON-ELSEVIER SCIENCE LTD
Rat aldose reductase-like protein (AKR1B14) is the ortholog of mouse vas deferens protein (AKR1B7) playing roles in detoxification of reactive aldehydes and synthesis of prostaglandin F2 alpha. The crystal structure of the binary complex (AKR1B14-NADPH) was determined at 1.86 angstrom resolution, and showed that the adenine ring and the 2 '-phosphate group of the coenzyme formed pi-stacking and electrostatic interactions with the imidazole ring and ND1 atom, respectively, of His269, which is not conserved in other aldose reductase-like proteins. The interactions were supported by site-directed mutagenesis of His269 to Arg, Phe and Met, which increased the K(m) for NADPH by 4, 7 and 127-fold, respectively. This is the first report of the tertiary structure of a rodent AKR1B7 ortholog, which describes the role of a novel dual interaction for the non-conserved His269 in coenzyme binding. (C) 2010 Elsevier Ltd. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bmcl.2010.11.086
- ISSN : 0960-894X
- PubMed ID : 21168333
- Web of Science ID : WOS:000285998000041