3O73

Crystal structure of quinone reductase 2 in complex with the indolequinone MAC627

3O73 の概要

• エントリーDOI: 10.2210/pdb3o73/pdb
• 関連するPDBエントリー: 1QR2
• 分子名称: Ribosyldihydronicotinamide dehydrogenase [quinone], ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: quinone reductase 2, nqo2, oxidoreductase, flavoprotein, indolequinone mac627, fad, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P16083
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56145.62

構造登録者

Dufour, M.,Yan, C.,Colucci, M.A.,Siegel, D.,Li, Y.,De Matteis, C.I.,Ross, D.,Moody, C.J. (登録日: 2010-07-30, 公開日: 2011-05-11, 最終更新日: 2023-09-06)

主引用文献

Dufour, M.,Yan, C.,Siegel, D.,Colucci, M.A.,Jenner, M.,Oldham, N.J.,Gomez, J.,Reigan, P.,Li, Y.,De Matteis, C.I.,Ross, D.,Moody, C.J.
Mechanism-Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition.
Chembiochem, 12:1203-1208, 2011

PubMed Abstract: A role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism-based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochemical studies confirmed the mechanism-based inhibition, whereas X-ray crystallography and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.

PubMed: 21506232
DOI: 10.1002/cbic.201100085

実験手法

X-RAY DIFFRACTION (2 Å)