Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2.

McLaughlin, L A, Niazi, U, Bibby, J, David, Jean-Philippe, Vontas, John, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247, Sutcliffe, M J and Paine, Mark ORCID: https://orcid.org/0000-0003-2061-7713 (2008) 'Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2.'. Insect molecular biology, Vol 17, Issue 2, pp. 125-135.

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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 microM; K(cat) = 1.5 min(-1). The IC(50) values of a wide range of compounds were measured. Pyrethroids cypermethrin and permethrin produced low IC(50) 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:	insecticide metabolism mosquito malaria
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Digital Object Identifer (DOI):	https://doi.org/10.1111/j.1365-2583.2007.00788.x
Depositing User:	Users 183 not found.
Date Deposited:	25 Aug 2010 12:56
Last Modified:	21 Nov 2024 12:05
URI:	https://archive.lstmed.ac.uk/id/eprint/1317

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