The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties

FEBS Lett. 2014 May 2;588(9):1666-72. doi: 10.1016/j.febslet.2014.02.063. Epub 2014 Mar 12.

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.

Keywords: Cooperativity; Dihydronicotinamide riboside; Resveratrol; rs1143684.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,6-Dichloroindophenol / chemistry
  • Amino Acid Substitution
  • Dinitrocresols / chemistry
  • Enzyme Inhibitors / chemistry
  • Enzyme Stability
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Kinetics
  • Niacinamide / analogs & derivatives
  • Niacinamide / chemistry
  • Oxidation-Reduction
  • Polymorphism, Single Nucleotide*
  • Proteolysis
  • Quinone Reductases / antagonists & inhibitors
  • Quinone Reductases / chemistry*
  • Quinone Reductases / genetics
  • Resveratrol
  • Stilbenes / chemistry

Substances

  • Dinitrocresols
  • Enzyme Inhibitors
  • Isoenzymes
  • Stilbenes
  • dihydronicotinamide
  • 4,6-dinitro-o-cresol
  • Niacinamide
  • 2,6-Dichloroindophenol
  • NRH - quinone oxidoreductase2
  • Quinone Reductases
  • Resveratrol