dihydronicotinamide and 4-6-dinitro-o-cresol

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.

Topics: 2,6-Dichloroindophenol; Amino Acid Substitution; Dinitrocresols; Enzyme Inhibitors; Enzyme Stability; Humans; Isoenzymes; Kinetics; Niacinamide; Oxidation-Reduction; Polymorphism, Single Nucleotide; Proteolysis; Quinone Reductases; Resveratrol; Stilbenes