1dla
From Proteopedia
NOVEL NADPH-BINDING DOMAIN REVEALED BY THE CRYSTAL STRUCTURE OF ALDOSE REDUCTASE
Overview
Aldose reductase is the first enzyme in the polyol pathway and catalyses the NADPH-dependent reduction of D-glucose to D-sorbitol. Under normal physiological conditions aldose reductase participates in osmoregulation, but under hyperglycaemic conditions it contributes to the onset and development of severe complications in diabetes. Here we present the crystal structure of pig lens aldose reductase refined to an R-factor of 0.232 at 2.5-A resolution. It exhibits a single domain folded in an eight-stranded parallel alpha/beta barrel, similar to that in triose phosphate isomerase and a score of other enzymes. Hence, aldose reductase does not possess the expected canonical dinucleotide-binding domain. Crystallographic analysis of the binding of 2'-monophospho-adenosine-5'-diphosphoribose, which competitively inhibits NADPH binding reveals that it binds into a cleft located at the C-terminal end of the strands of the alpha/beta barrel. This represents a new type of binding for nicotinamide adenine dinucleotide coenzymes.
About this Structure
1DLA is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Novel NADPH-binding domain revealed by the crystal structure of aldose reductase., Rondeau JM, Tete-Favier F, Podjarny A, Reymann JM, Barth P, Biellmann JF, Moras D, Nature. 1992 Jan 30;355(6359):469-72. PMID:1734286 Page seeded by OCA on Fri May 2 13:58:50 2008
