Abstract
There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings.
Highlights
IntroductionNAD(P)H quinone oxidoreductase 1 (NQO1, DTdiaphorase, EC 1.6.5.2) is the better characterised of the two [1,2]
There are two members of the quinone oxidoreductase family in humans
NAD(P)H quinone oxidoreductase 1 (NQO1, DTdiaphorase, EC 1.6.5.2) is the better characterised of the two [1,2]. This enzyme is believed to be involved in vitamin K metabolism and in reducing the cellular quinone concentration, preventing build-up of reactive oxygen species [3,4,5]
Summary
NAD(P)H quinone oxidoreductase 1 (NQO1, DTdiaphorase, EC 1.6.5.2) is the better characterised of the two [1,2]. This enzyme is believed to be involved in vitamin K metabolism and in reducing the cellular quinone concentration, preventing build-up of reactive oxygen species [3,4,5]. Its up-regulation in some cancer cells and its role in the conversion of some prodrugs (e.g. mitomycin c) to their pharmacologically active forms has resulted in considerable interest in targeting this enzyme for the development of novel cancer chemotherapies [5,12,13,14,15,16].
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