1D4A

CRYSTAL STRUCTURE OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE AT 1.7 A RESOLUTION

1D4A の概要

• エントリーDOI: 10.2210/pdb1d4a/pdb
• 関連するPDBエントリー: 1QR2 1QRD 2QR2
• 分子名称: QUINONE REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: flavoprotein, rossmann fold, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P15559
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 126247.85

構造登録者

Faig, M.,Bianchet, M.A.,Chen, S.,Winski, S.,Ross, D.,Amzel, L.M. (登録日: 1999-10-01, 公開日: 1999-10-15, 最終更新日: 2024-02-07)

主引用文献

Faig, M.,Bianchet, M.A.,Talalay, P.,Chen, S.,Winski, S.,Ross, D.,Amzel, L.M.
Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release.
Proc.Natl.Acad.Sci.USA, 97:3177-3182, 2000

PubMed Abstract: NAD(P)H/quinone acceptor oxidoreductase (QR1, NQO1, formerly DT-diaphorase; EC ) protects animal cells from the deleterious and carcinogenic effects of quinones and other electrophiles. In this paper we report the apoenzyme structures of human (at 1.7-A resolution) and mouse (2.8 A) QR1 and the complex of the human enzyme with the substrate duroquinone (2.5 A) (2,3,5, 6-tetramethyl-p-benzoquinone). In addition to providing a description and rationale of the structural and catalytic differences among several species, these structures reveal the changes that accompany substrate or cofactor (NAD) binding and release. Tyrosine-128 and the loop spanning residues 232-236 close the binding site, partially occupying the space left vacant by the departing molecule (substrate or cofactor). These changes highlight the exquisite control of access to the catalytic site that is required by the ping-pong mechanism in which, after reducing the flavin, NAD(P)(+) leaves the catalytic site and allows substrate to bind at the vacated position. In the human QR1-duroquinone structure one ring carbon is significantly closer to the flavin N5, suggesting a direct hydride transfer to this atom.

PubMed: 10706635
DOI: 10.1073/pnas.050585797

実験手法

X-RAY DIFFRACTION (1.7 Å)