NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places
Metadata
Show full item recordEditorial
Portland Press
Date
2019Referencia bibliográfica
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).
Sponsorship
This work was supported by the Junta de Andalucía [grant number P11-CTS-07187 (to A.L.P.)].Abstract
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.