کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1371092 981838 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the role of His269 in coenzyme binding by site-directed mutagenesis
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the role of His269 in coenzyme binding by site-directed mutagenesis
چکیده انگلیسی

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 F2α. The crystal structure of the binary complex (AKR1B14-NADPH) was determined at 1.86 Å resolution, and showed that the adenine ring and the 2′-phosphate group of the coenzyme formed π-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 Km 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.

Superimposition of the structures of AKR1B14 (magenta) and AKR1B1 (green) in the vicinity of the 2′-phosphate adenosine moiety of NADPH (blue).Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 2, 15 January 2011, Pages 801–804
نویسندگان
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