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

Clare F. Megarity; James R E Gill; M. Clare Caraher; Ian J. Stratford; Karen A. Nolan; David J. Timson

doi:10.1016/j.febslet.2014.02.063

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

Clare F. Megarity, James R E Gill, M. Clare Caraher, Ian J. Stratford, Karen A. Nolan, David J. Timson

Research output: Contribution to journal › Article › peer-review

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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	1666-1672
Number of pages	7
Journal	FEBS Letters
Volume	588
Issue number	9
Early online date	12 Mar 2014
DOIs	https://doi.org/10.1016/j.febslet.2014.02.063
Publication status	Published - 2 May 2014

Keywords

Cooperativity
Dihydronicotinamide riboside
Resveratrol
rs1143684

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10.1016/j.febslet.2014.02.063

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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. {\textcopyright} 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",

keywords = "Cooperativity, Dihydronicotinamide riboside, Resveratrol, rs1143684",

author = "Megarity, {Clare F.} and Gill, {James R E} and {Clare Caraher}, M. and Stratford, {Ian J.} and Nolan, {Karen A.} and Timson, {David J.}",

year = "2014",

month = may,

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doi = "10.1016/j.febslet.2014.02.063",

language = "English",

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TY - JOUR

T1 - The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties

AU - Megarity, Clare F.

AU - Gill, James R E

AU - Clare Caraher, M.

AU - Stratford, Ian J.

AU - Nolan, Karen A.

AU - Timson, David J.

PY - 2014/5/2

Y1 - 2014/5/2

N2 - 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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

AB - 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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KW - Cooperativity

KW - Dihydronicotinamide riboside

KW - Resveratrol

KW - rs1143684

UR - http://www.sciencedirect.com/science/article/pii/S0014579314001999

U2 - 10.1016/j.febslet.2014.02.063

DO - 10.1016/j.febslet.2014.02.063

M3 - Article

C2 - 24631540

VL - 588

SP - 1666

EP - 1672

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

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

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Keywords

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