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

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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.

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 - 02 May 2014

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10.1016/j.febslet.2014.02.063

The two common polymorphic forms of human NRH-quinone
© 2014 The Authors This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
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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.",

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AU - Megarity, Clare F.

AU - Gill, James R.E.

AU - Caraher, M. Clare

AU - Stratford, Ian J.

AU - Nolan, Karen A.

AU - Timson, David J.

PY - 2014/5/2

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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.

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DO - 10.1016/j.febslet.2014.02.063

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

Abstract

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