1DLA

NOVEL NADPH-BINDING DOMAIN REVEALED BY THE CRYSTAL STRUCTURE OF ALDOSE REDUCTASE

1DLA の概要

• エントリーDOI: 10.2210/pdb1dla/pdb
• 分子名称: ALDOSE REDUCTASE (1 entity in total)
• 機能のキーワード: oxidoreductase(nadp)
• 由来する生物種: Sus scrofa (pig)
• 細胞内の位置: Cytoplasm: P80276
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 142843.70

構造登録者

Rondeau, J.-M.,Tete-Favier, F.,Podjarny, A.,Reymann, J.-M.,Barth, P.,Biellmann, J.-F.,Moras, D. (登録日: 1993-02-08, 公開日: 1994-04-30, 最終更新日: 2024-02-07)

主引用文献

Rondeau, J.M.,Tete-Favier, F.,Podjarny, A.,Reymann, J.M.,Barth, P.,Biellmann, J.F.,Moras, D.
Novel NADPH-binding domain revealed by the crystal structure of aldose reductase.
Nature, 355:469-472, 1992

PubMed Abstract: 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.

PubMed: 1734286
DOI: 10.1038/355469a0

実験手法

X-RAY DIFFRACTION (3 Å)