1ABN

THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX

1ABN の概要

• エントリーDOI: 10.2210/pdb1abn/pdb
• 分子名称: ALDOSE REDUCTASE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (2 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P15121
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36496.50

構造登録者

Borhani, D.W.,Harter, T.M.,Petrash, J.M. (登録日: 1992-09-03, 公開日: 1994-01-31, 最終更新日: 2024-02-07)

主引用文献

Borhani, D.W.,Harter, T.M.,Petrash, J.M.
The crystal structure of the aldose reductase.NADPH binary complex.
J.Biol.Chem., 267:24841-24847, 1992

PubMed Abstract: Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure.

PubMed: 1447221

実験手法

X-RAY DIFFRACTION (2.4 Å)