Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

L. A. McLaughlin; U. Niazi; J. Bibby; J. P. David; J. Vontas; J. Hemingway; H. Ranson; M. J. Sutcliffe; M. J I Paine

doi:10.1111/j.1365-2583.2007.00788.x

Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

L. A. McLaughlin, U. Niazi, J. Bibby, J. P. David, J. Vontas, J. Hemingway, H. Ranson, M. J. Sutcliffe, M. J I Paine

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

Abstract

Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae. We have expressed CYP6Z2 in Escherichia coli and produced a structural model in order to examine its role in detoxification. E. coli membranes co-expressing CYP6Z2 and An. gambiae P450 reductase (AgCPR) catalysed the dealkylation of benzyloxyresorufin with kinetic parameters K m = 0.13 μM; Kcat = 1.5 min-1. The IC 50 values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC50 values, but were not metabolized. Plant flavanoids were the most potent inhibitors. Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo-protective role during the herbivorous phase of the life-cycle. © 2008 The Authors.

Original language	English
Pages (from-to)	125-135
Number of pages	10
Journal	Insect Molecular Biology
Volume	17
Issue number	2
DOIs	https://doi.org/10.1111/j.1365-2583.2007.00788.x
Publication status	Published - Apr 2008

Keywords

Insecticide metabolism
Malaria
Mosquito
P450
P450 reductase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/j.1365-2583.2007.00788.x

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title = "Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2",

abstract = "Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae. We have expressed CYP6Z2 in Escherichia coli and produced a structural model in order to examine its role in detoxification. E. coli membranes co-expressing CYP6Z2 and An. gambiae P450 reductase (AgCPR) catalysed the dealkylation of benzyloxyresorufin with kinetic parameters K m = 0.13 μM; Kcat = 1.5 min-1. The IC 50 values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC50 values, but were not metabolized. Plant flavanoids were the most potent inhibitors. Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo-protective role during the herbivorous phase of the life-cycle. {\textcopyright} 2008 The Authors.",

keywords = "Insecticide metabolism, Malaria, Mosquito, P450, P450 reductase",

author = "McLaughlin, {L. A.} and U. Niazi and J. Bibby and David, {J. P.} and J. Vontas and J. Hemingway and H. Ranson and Sutcliffe, {M. J.} and Paine, {M. J I}",

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language = "English",

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T1 - Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

AU - McLaughlin, L. A.

AU - Niazi, U.

AU - Bibby, J.

AU - David, J. P.

AU - Vontas, J.

AU - Hemingway, J.

AU - Ranson, H.

AU - Sutcliffe, M. J.

AU - Paine, M. J I

PY - 2008/4

Y1 - 2008/4

N2 - Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae. We have expressed CYP6Z2 in Escherichia coli and produced a structural model in order to examine its role in detoxification. E. coli membranes co-expressing CYP6Z2 and An. gambiae P450 reductase (AgCPR) catalysed the dealkylation of benzyloxyresorufin with kinetic parameters K m = 0.13 μM; Kcat = 1.5 min-1. The IC 50 values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC50 values, but were not metabolized. Plant flavanoids were the most potent inhibitors. Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo-protective role during the herbivorous phase of the life-cycle. © 2008 The Authors.

AB - Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae. We have expressed CYP6Z2 in Escherichia coli and produced a structural model in order to examine its role in detoxification. E. coli membranes co-expressing CYP6Z2 and An. gambiae P450 reductase (AgCPR) catalysed the dealkylation of benzyloxyresorufin with kinetic parameters K m = 0.13 μM; Kcat = 1.5 min-1. The IC 50 values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC50 values, but were not metabolized. Plant flavanoids were the most potent inhibitors. Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo-protective role during the herbivorous phase of the life-cycle. © 2008 The Authors.

KW - Insecticide metabolism

KW - Malaria

KW - Mosquito

KW - P450

KW - P450 reductase

U2 - 10.1111/j.1365-2583.2007.00788.x

DO - 10.1111/j.1365-2583.2007.00788.x

M3 - Article

VL - 17

SP - 125

EP - 135

JO - Insect Molecular Biology

JF - Insect Molecular Biology

SN - 0962-1075

IS - 2

ER -

Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

Abstract

Keywords

UN SDGs

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