观察到人类NAD(P)H:quinone oxidoreductase 1 (NQO1)在酶的催化位点具有大的构象杂质。本文报道了NQO1与苯甲基磺酰氟(PMSF)共结的X射线结构，分辨率为1.6 Å。活性测定证实，尽管PMSF与催化位点的Tyr128残基共价结合，但并未使NQO1的活性丧失。这可能表明PMSF分子并不能减少Tyr128的高柔性，从而使NADH和DCPIP底物能够与酶结合。我们的结果表明，以小的共价结合分子靶向NQO1功能中的关键残基Tyr128可能并不是一种良好的药物发现策略来抑制该酶。本文受版权保护。版权所有。

A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X-ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6 Å resolution. Activity assays confirmed that, despite being covalently bound to the Tyr128 residue at the catalytic site, PMSF did not abolish NQO1 activity. This may indicate that the PMSF molecule does not reduce the high flexibility of Tyr128, thus allowing NADH and DCPIP substrates to bind to the enzyme. Our results show that targeting Tyr128, a key residue in NQO1 function, with small covalently bound molecules could possibly not be a good drug discovery strategy to inhibit this enzyme.This article is protected by copyright. All rights reserved.