1QBG

CRYSTAL STRUCTURE OF HUMAN DT-DIAPHORASE (NAD(P)H OXIDOREDUCTASE)

1QBG の概要

• エントリーDOI: 10.2210/pdb1qbg/pdb
• 分子名称: NAD(P)H DEHYDROGENASE [QUINONE] 1, FLAVIN-ADENINE DINUCLEOTIDE (2 entities in total)
• 機能のキーワード: quinone, fad, oxidoreductase, dt-diaphorase
• 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: 126019.66

構造登録者

Skelly, J.V.,Sanderson, M.R.,Suter, D.A.,Baumann, U.,Gregory, D.S.,Bennett, M.,Hobbs, S.M.,Neidle, S. (登録日: 1999-04-20, 公開日: 2000-04-24, 最終更新日: 2024-02-14)

主引用文献

Skelly, J.V.,Sanderson, M.R.,Suter, D.A.,Baumann, U.,Read, M.A.,Gregory, D.S.,Bennett, M.,Hobbs, S.M.,Neidle, S.
Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954).
J.Med.Chem., 42:4325-4330, 1999

PubMed Abstract: The crystal structure of human DT-diaphorase (NAD(P)H oxidoreductase (quinone); EC 1.6.99.2) has been determined to 2.3 A resolution. There are only minor differences in shape and volume between the active sites of the rat and human enzymes and in the hydrophobic environment in the vicinity of the substrate. The isoalloxazine ring of the bound FAD is more buried in the human structure. Molecular modeling was used to examine optimal positions for the antitumor prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) in both the human and rat enzyme active sites. This suggests that the position of CB1954 in the active site of the human enzyme is very similar to that in the rat, although there are detailed differences in the predicted patterns of hydrogen bonding between side chains and the drug. Some of the differences are a consequence of the shift in position for the FAD molecule and may contribute to the observed differences in rate of the two-electron reduction of CB1954.

PubMed: 10543876
DOI: 10.1021/jm991060m

実験手法

X-RAY DIFFRACTION (2.3 Å)