Structure-function studies of DT-diaphorase (NQO1) and NRH:quinone oxidoreductase (NQO2)
Structure-function studies of DT-diaphorase (NQO1) and NRH:quinone oxidoreductase (NQO2)
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DOI：
10.1016/s0891-5849(00)00308-7
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发表时间：
2000-08-01
影响因子：
7.4
通讯作者：
Knox, R
中科院分区：
文献类型：
--
作者：
Chen, S;Wu, KB;Knox, R
DT-diaphorase，也被称为NQO1或NAD(P)H：醌受体氧化还原酶，是一种黄酮类蛋白，使用NADH或NADPH作为电子供体，催化醌和醌类化合物的双电子还原为对苯二酚。NRH (dihydronicotinamide riboside)：醌氧化还原酶，又称NQO2，与DT-diaphorase具有较高的核苷酸序列同一性，被认为是DT-diaphorase的同工酶。这些酶将两个电子转移到醌上，从而形成对苯二酚产物，而不会积累解离的半醌。通过稳定快速反应动力学实验确定了dt -脱氢酶的反应机理。此外，嵌合和定点诱变实验已经进行，以确定两种同工酶之间的催化差异的分子基础，并确定与酶的各种抑制剂相互作用的关键氨基酸残基。此外，对天然突变体Pro-187 - Ser （P187S）进行了功能研究。对这些调查所得的结果进行了总结和讨论。(C) 2000 Elsevier Science Inc.；
DT-diaphorase, also referred to as NQO1 or NAD(P)H: quinone acceptor oxidoreductase, is a flavoprotein that catalyzes the two-electron reduction of quinones and quinonoid compounds to hydroquinones, using either NADH or NADPH as the electron donor. NRH (dihydronicotinamide riboside): quinone oxidoreductase, also referred to as NQO2, has a high nucleotide sequence identity to DT-diaphorase and is considered to he an isozyme of DT-diaphorase. These enzymes transfer two electrons to a quinone, resulting in the formation of a hydroquinone product without the accumulation of a dissociated semiquinone. Steady and rapid-reaction kinetic experiments have been performed to determine the reaction mechanism of DT-diaphorase. Furthermore, chimeric and site-directed mutagenesis experiments have been performed to determine the molecular basis of the catalytic differences between the two isozymes and to identify the critical amino acid residues that interact with various inhibitors of the enzymes. In addition, functional studies of a natural occurring mutant Pro-187 to Ser (P187S) have been carried out. Results obtained from these investigations are summarized and discussed. (C) 2000 Elsevier Science Inc.