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Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

Mclaughlin, L.A., Niazi, U., Bibby, J., David, Jean-Philippe, Vontas, John, Hemingway, Janet ORCID:, Ranson, Hilary ORCID:, Sutcliffe, M.J. and Paine, Mark ORCID: (2008) 'Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2'. Insect Molecular Biology, Vol 17, Issue 2, pp. 125-135.

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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 mu M; K-cat = 1.5 min(-1). The IC50 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.

Item Type: Article
Uncontrolled Keywords: p450 insecticide metabolism mosquito malaria p450 reductase insecticide resistance escherichia-coli malaria vector p450 sequences docking binding strain
Subjects: QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department: Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI):
Depositing User: Users 183 not found.
Date Deposited: 10 Aug 2010 13:12
Last Modified: 30 Aug 2019 17:04


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