NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places Pey Rodríguez, Ángel Luis Megarity, Clare F. Timson, David J. NAD(P)H quinone oxidoreductase 1 (NQO1) catalyses the two electron reduction of quinones and a wide range of other organic compounds. Its physiological role is believed to be partly the reduction of free radical load in cells and the detoxification of xenobiotics. It also has non-enzymatic functions stabilising a number of cellular regulators including p53. Functionally, NQO1 is a homodimer with two active sites formed from residues from both polypeptide chains. Catalysis proceeds via a substituted enzyme mechanism involving a tightly bound FAD cofactor. Dicoumarol and some structurally related compounds act as competitive inhibitors of NQO1. There is some evidence for negative cooperativity in quinine oxidoreductases which is most likely to be mediated at least in part by alterations to the mobility of the protein. Human NQO1 is implicated in cancer. It is often over-expressed in cancer cells and as such is considered as a possible drug target. Interestingly, a common polymorphic form of human NQO1, p.P187S, is associated with an increased risk of several forms of cancer. This variant has much lower activity than the wild-type, primarily due to its substantially reduced affinity for FAD which results from lower stability. This lower stability results from inappropriate mobility of key parts of the protein. Thus, NQO1 relies on correct mobility for normal function, but inappropriate mobility results in dysfunction and may cause disease. 2020-02-21T09:34:00Z 2020-02-21T09:34:00Z 2019 info:eu-repo/semantics/article Pey, A. L., Megarity, C. F., & Timson, D. J. (2019). NAD (P) H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places. Bioscience reports, 39(1). http://hdl.handle.net/10481/59801 10.1042/BSR20180459 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Portland Press