title: The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties.
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.
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Clare F
authors.initials: CF
authors.lastname: Megarity
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: James R E
authors.initials: JR
authors.lastname: Gill
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Manchester Pharmacy School, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: M Clare
authors.initials: MC
authors.lastname: Caraher
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Stratford
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Nolan
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: d.timson@qub.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Timson
mesh_terms: D015086:2,6-Dichloroindophenol / Q000737:chemistry; D019943:Amino Acid Substitution; D004138:Dinitrocresols / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D004795:Enzyme Stability; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D059748:Proteolysis; D011808:Quinone Reductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry
chemical_list: D004138:Dinitrocresols; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013267:Stilbenes; C015145:dihydronicotinamide; C024132:4,6-dinitro-o-cresol; D009536:Niacinamide; D015086:2,6-Dichloroindophenol; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D000077185:Resveratrol
keywords: Cooperativity; Dihydronicotinamide riboside; Resveratrol; rs1143684