Structure of the His269Arg mutant of the rat aldose reductase-like protein AKR1B14 complexed with NADPH.

ABSTRACT: Rat aldose reductase-like protein (AKR1B14) is an orthologue of mouse vas deferens protein (AKR1B7) and plays roles in the detoxification of reactive aldehydes and synthesis of prostaglandin F(2α). Here, the 1.87 Å resolution crystal structure of the His269Arg mutant of AKR1B14 complexed with NADPH is described and shows that the negatively charged 2'-phosphate group of the coenzyme forms an ionic interaction with the positively charged guanidinium group of Arg269 that is also observed in the human aldose reductase (AKR1B1) structure. Previous experiments on the site-directed mutagenesis of His269 to Arg, Phe and Met revealed fourfold, sevenfold and 127-fold increases in the K(m) for NADPH, respectively, which are in agreement with the present molecular-modelling and X-ray crystallographic

SUBMITTER: Sundaram K 

PROVIDER: S-EPMC3325806 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature