Islam Faiza, Shilton Brian
Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Biochem J. 2025 Mar 11;482(6):BCJ20240103. doi: 10.1042/BCJ20240103.
Quinone reductase 2 (NQO2) is a FAD-linked enzyme that cannot use the common reducing cofactors, NADH and NADPH, for efficient catalysis. This is unusual for an oxidoreductase, particularly since it is a member of a large family of enzymes that all use NAD(P)H efficiently to catalyse the two-electron reduction in quinones and other electrophiles. The inability of NQO2 to use NAD(P)H efficiently raises questions about its cellular function: it remains unclear whether the main cellular role of NQO2 is the catalytic reduction in quinones or whether it is a pseudo-enzyme with other roles such as cell signalling. Intriguingly, NQO2 has been identified as an off-target interactor with over 30 kinase inhibitors and other drugs and natural products. The interaction between NQO2 and kinase-targeted drugs is particularly intriguing because it suggests that NQO2 may be contributing to the cellular effects of these drugs. In this review, we will discuss the enzymatic properties of NQO2, its structure and complexes with various drugs and small molecules, potential cellular roles, and some of the enigmatic findings that make this molecule so interesting and worthy of further investigation.
醌还原酶2（NQO2）是一种与黄素腺嘌呤二核苷酸（FAD）相连的酶，它不能利用常见的还原性辅酶NADH和NADPH进行高效催化。这对于氧化还原酶来说是不寻常的，尤其是因为它是一个大家族的成员，而该家族中的所有酶都能有效地利用NAD(P)H催化醌类和其他亲电试剂的双电子还原反应。NQO2无法有效利用NAD(P)H这一情况引发了关于其细胞功能的疑问：目前尚不清楚NQO2在细胞中的主要作用是催化醌类的还原反应，还是作为一种具有其他作用（如细胞信号传导）的假酶。有趣的是，NQO2已被确定为与30多种激酶抑制剂以及其他药物和天然产物的脱靶相互作用分子。NQO2与激酶靶向药物之间的相互作用尤其引人关注，因为这表明NQO2可能对这些药物的细胞效应有影响。在本综述中，我们将讨论NQO2的酶学性质、其结构以及与各种药物和小分子的复合物、潜在的细胞作用，以及一些使该分子如此有趣且值得进一步研究的神秘发现。
