Molecular analysis of multiple cytochrome P450 genes from the malaria vector, <i>Anopheles gambiae</i>

Ranson, Hilary; Nikou, Dimitra; Hutchinson, MN; Wang, X.; Roth, Charles W.; Hemingway, Janet; Collins, Frank H.

doi:10.1046/j.1365-2583.2002.00350.x

Cited by 66 publications

(51 citation statements)

References 21 publications

(29 reference statements)

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“…The sequences of CYP6Z1 (GenBank accession no. AF487535) from the RSP-ST strain of mosquito (41,42) and CYP6Z2 (GenBank accession no. XP 317252) from the PEST strain (ref.…”

Section: Methodsmentioning

confidence: 99%

“…Sequence Variants. With the CYP6Z1 model developed from a cDNA sequence available from the permethrin-and DDT-resistant RSP-ST strain (41,42) and the CYP6Z2 model developed from a cDNA sequence available from the insecticide-susceptible PEST strain, we further evaluated a number of sequence variants deposited in the GenBank database for other Anopheles strains. Alignment of the CYP6Z1 RSP-ST sequence with the CYP6Z1 sequence expressed from the G3 strain identified four differences (S107N, R327Q, T346N, and V492A listed with RSP-ST residue first and G3 residue second).…”

Section: Docking Of Prospective Substrates Into the Cyp6z1 And Cyp6z2mentioning

confidence: 99%

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Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT

Chiu

Wen

Rupasinghe

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

171

138

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One of the challenges faced in malarial control is the acquisition of insecticide resistance that has developed in mosquitoes that are vectors for this disease. Anopheles gambiae, which has been the major mosquito vector of the malaria parasite Plasmodium falciparum in Africa, has over the years developed resistance to insecticides including dieldrin, 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), and pyrethroids. Previous microarray studies using fragments of 230 An. gambiae genes identified five P450 loci, including CYP4C27, CYP4H15, CYP6Z1, CYP6Z2, and CYP12F1, that showed significantly higher expression in the DDT-resistant ZAN/U strain compared with the DDT-susceptible Kisumu strain. To predict whether either of the CYP6Z1 and CYP6Z2 proteins might potentially metabolize DDT, we generated and compared molecular models of these two proteins with and without DDT docked in their catalytic sites. This comparison indicated that, although these two CYP6Z proteins share high sequence identity, their metabolic profiles were likely to differ dramatically from the larger catalytic site of CYP6Z1, potentially involved in DDT metabolism, and the more constrained catalytic site of CYP6Z2, not likely to metabolize DDT. Heterologous expressions of these proteins have corroborated these predictions: only CYP6Z1 is capable of metabolizing DDT. Overlays of these models indicate that slight differences in the backbone of SRS1 and variations of side chains in SRS2 and SRS4 account for the significant differences in their catalytic site volumes and DDT-metabolic capacities. These data identify CYP6Z1 as one important target for inhibitor design aimed at inactivating insecticide-metabolizing P450s in natural populations of this malarial mosquito.cytochrome P450 monooxygenases ͉ insecticides ͉ plant allelochemicals I n 2004, the World Health Organization reported that up to 2.7 million people die of malaria every year with 80-90% of these deaths occurring in Africa (ref. 1 and www.africanfront.com/ AIDS1.php). Many prevention and treatment strategies have been developed to tackle this life-threatening disease from the side of the mosquito vector and that of the human host (2, 3). These range from antimalarial drugs to indoor spraying of insecticides and use of bed nets treated with pyrethroid insecticides. Although these practices have helped reduce human mortality, various issues have emerged with mosquito vectors developing insecticide resistance and parasites developing drug resistance. Both of these significantly reduce the efficacy of current malarial prevention and treatment practices (2, 4-8).The development of insecticide resistance in mosquito vectors is illustrated by Anopheles gambiae, which has been the major mosquito vector of the malaria parasite Plasmodium falciparum in Africa (4, 6). Throughout the years, people have reported Anopheles resistance (albeit low-level resistance) to various insecticides including dieldrin (a cyclodiene-type insecticide), 1,1-bis(pchlorophenyl)-2,2,2-trichloroethane (DDT), and pe...

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“…The sequences of CYP6Z1 (GenBank accession no. AF487535) from the RSP-ST strain of mosquito (41,42) and CYP6Z2 (GenBank accession no. XP 317252) from the PEST strain (ref.…”

Section: Methodsmentioning

confidence: 99%

Section: Docking Of Prospective Substrates Into the Cyp6z1 And Cyp6z2mentioning

confidence: 99%

Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT

Chiu

Wen

Rupasinghe

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

171

138

View full text Add to dashboard Cite

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“…As shown in Figure 4, the Ciona The intergenic regions between genes CI50 and CI85, and between CI85 and CI43 are 550 bp and 772 bp, respectively. Gene clusters have been previously described in the CYP3s and in CYP6s and CYP9s (Finta and Zaphiropoulos, 2000;Ranson et al, 2002). Genes in these clusters are separated by intergenic regions ranging from a few tens, to several thousand bps.…”

Section: Cloning Of Novel Tunicate Cyp Genesmentioning

confidence: 99%

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Verslycke

Goldstone

Stegeman

2006

Molecular Phylogenetics and Evolution

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Cytochromes P450 (CYPs) form a gene superfamily involved in the biotransformation of numerous endogenous and exogenous natural and synthetic compounds. In humans, CYP3A4 is regarded as one of the most important CYPs due to its abundance in liver and its capacity to metabolize more than 50% of all clinically used drugs. It has been suggested that all CYP3s arose from a common ancestral gene lineage that diverged between 800 and 1100 million years ago, before the deuterostome-protostome split. While CYP3s are well known in mammals and have been described in lower vertebrates, they have not been reported in non-vertebrate deuterostomes. Members of the genus Ciona belong to the tunicates, whose lineage is thought to be the most basal among the chordates, and from which the vertebrate line diverged. Here we describe the cloning, exon-intron structure, phylogeny, and estimated expression of four novel genes from Ciona intestinalis. We also describe the gene structure and phylogeny of homologous genes in Ciona savignyi. Comparing these genes with other members of the CYP clan 3, show that the Ciona sequences bear remarkable similarity to vertebrate CYP3A genes, and may be an early deuterostome CYP3 line.

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“…While attention on CYP in aquatic invertebrates has focused primarily on its application in pollution monitoring, the basic characteristics, such as levels, activities, structure and regulation, are relatively unknown in most crustaceans (Solé and Livingstone, 2005). In insect models such as Drosophila melanogaster and Anopheles gambiae, genome sequencing has recently allowed the identification of all putative CYPs (Tijet et al, 2001;Ranson et al, 2002) with two families (CYP4 and CYP6) being the most diverse. Few studies have dealt with CYP identification and phylogeny in crustaceans, but the CYP4 family also appears very diverse, and CYP4 expression in daphnids was shown to be related to environmental xenobiotic concentrations (David et al, 2003).…”

Section: This Issue)mentioning

confidence: 99%

Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

et al. 2007

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Investigative efforts into the potential endocrine-disrupting effects of chemicals have mainly concentrated on vertebrates, with significantly less attention paid to understanding potential endocrine disruption in the invertebrates. Given that invertebrates account for at least 95% of all known animal species and are critical to ecosystem structure and function, it remains essential to close this gap in knowledge and research. The lack of progress regarding endocrine disruption in invertebrates is still largely due to: (1) our ignorance of mode-of-action, physiological control, and hormone structure and function in invertebrates; (2) lack of a standardized invertebrate assay; (3) the irrelevance to most invertebrates of the proposed activity-based biological indicators for endocrine disruptor exposure (androgen, estrogen and thyroid); (4) limited field studies. Past and ongoing research efforts using the standard invertebrate toxicity test model, the mysid shrimp, have aimed at addressing some of these issues. The present review serves as an update to a previous publication on the use of mysid shrimp for the evaluation of endocrine disruptors (Verslycke et al., 2004a). It summarizes recent investigative efforts that have significantly advanced our understanding of invertebrate-specific endocrine toxicity, population modeling, field studies, and transgeneration standard test development using the mysid model.

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Molecular analysis of multiple cytochrome P450 genes from the malaria vector, Anopheles gambiae

Cited by 66 publications

References 21 publications

Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT

Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

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