3o3r

Publication Abstract from PubMed

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 F(2alpha). The crystal structure of the binary complex (AKR1B14-NADPH) was determined at 1.86A 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.

Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the role of His269 in coenzyme binding by site-directed mutagenesis.,Sundaram K, Dhagat U, Endo S, Chung R, Matsunaga T, Hara A, El-Kabbani O Bioorg Med Chem Lett. 2011 Jan 15;21(2):801-4. Epub 2010 Nov 24. PMID:21168333^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.