Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2
Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2
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DOI：
10.1111/j.1365-2583.2007.00788.x
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发表时间：
2008-04-01
影响因子：
2.6
通讯作者：
Paine, M. J. I.
中科院分区：
文献类型：
--
作者：
Mclaughlin, L. A.;Niazi, U.;Paine, M. J. I.
三个CYP 6 Z基因与冈比亚按蚊中的一个主要拟除虫菊酯抗性位点相关。我们在大肠杆菌中表达了CYP 6 Z2，并建立了一个结构模型，以研究其在解毒中的作用。E.共表达CYP 6 Z2和An.冈比亚P450还原酶（AgCPR）催化苄氧基试卤灵的脱烷基化，动力学参数K-m = 0.13 μ M; K-cat = 1.5 min（-1）。测量了多种化合物的IC 50值。拟除虫菊酯氯氰菊酯和氯菊酯产生低IC 50值，但不代谢。植物黄酮类化合物是最有效的抑制剂。几种化合物被证明是底物，表明CYP 6 Z2具有广泛的底物特异性，并在生命周期的草食性阶段发挥重要的化学保护作用。
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.