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Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2

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dc.contributor.author McLaughlin, LA en
dc.contributor.author Niazi, U en
dc.contributor.author Bibby, J en
dc.contributor.author David, J-P en
dc.contributor.author Vontas, J en
dc.contributor.author Hemingway, J en
dc.contributor.author Ranson, H en
dc.contributor.author Sutcliffe, MJ en
dc.contributor.author Paine, MJI en
dc.date.accessioned 2014-06-06T06:48:22Z
dc.date.available 2014-06-06T06:48:22Z
dc.date.issued 2008 en
dc.identifier.issn 09621075 en
dc.identifier.uri http://dx.doi.org/10.1111/j.1365-2583.2007.00788.x en
dc.identifier.uri http://62.217.125.90/xmlui/handle/123456789/4113
dc.subject Insecticide metabolism en
dc.subject Malaria en
dc.subject Mosquito en
dc.subject P450 en
dc.subject P450 reductase en
dc.subject.other acridine orange en
dc.subject.other cytochrome P450 en
dc.subject.other DNA en
dc.subject.other insecticide en
dc.subject.other isoenzyme en
dc.subject.other pyrethroid en
dc.subject.other recombinant protein en
dc.subject.other amino acid sequence en
dc.subject.other animal en
dc.subject.other Anopheles gambiae en
dc.subject.other article en
dc.subject.other biosynthesis en
dc.subject.other chemical structure en
dc.subject.other chemistry en
dc.subject.other disease carrier en
dc.subject.other drug antagonism en
dc.subject.other enzymology en
dc.subject.other Escherichia coli en
dc.subject.other genetics en
dc.subject.other IC 50 en
dc.subject.other insecticide resistance en
dc.subject.other metabolism en
dc.subject.other molecular cloning en
dc.subject.other molecular genetics en
dc.subject.other polymerase chain reaction en
dc.subject.other sequence alignment en
dc.subject.other Acridine Orange en
dc.subject.other Amino Acid Sequence en
dc.subject.other Animals en
dc.subject.other Anopheles gambiae en
dc.subject.other Cloning, Molecular en
dc.subject.other Cytochrome P-450 Enzyme System en
dc.subject.other DNA en
dc.subject.other Escherichia coli en
dc.subject.other Inhibitory Concentration 50 en
dc.subject.other Insect Vectors en
dc.subject.other Insecticide Resistance en
dc.subject.other Insecticides en
dc.subject.other Isoenzymes en
dc.subject.other Models, Molecular en
dc.subject.other Molecular Sequence Data en
dc.subject.other Polymerase Chain Reaction en
dc.subject.other Pyrethrins en
dc.subject.other Recombinant Proteins en
dc.subject.other Sequence Alignment en
dc.subject.other Anopheles gambiae en
dc.subject.other Escherichia coli en
dc.title Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2 en
heal.type journalArticle en
heal.identifier.primary 10.1111/j.1365-2583.2007.00788.x en
heal.publicationDate 2008 en
heal.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. en
heal.journalName Insect Molecular Biology en
dc.identifier.issue 2 en
dc.identifier.volume 17 en
dc.identifier.doi 10.1111/j.1365-2583.2007.00788.x en
dc.identifier.spage 125 en
dc.identifier.epage 135 en


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