Homology modelling of <i>Drosophila</i> cytochrome P450 enzymes associated with insecticide resistance

Pest Management Science - Tập 66 Số 10 - Trang 1106-1115 - 2010
Robert T. Jones1, Saskia E. Bakker1, Deborah B. Stone1, Sally N Shuttleworth1, Sam Boundy1, Caroline McCart1, Phillip J. Daborn2, Richard H. ffrench‐Constant3,4,5, Jean van den Elsen1,4,5
1Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
2Centre for Environmental Stress and Adaptation Research (CESAR), Department of Genetics, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia
3Centre for Ecology and Conservation, University of Exeter, Cornwall Campus, Penryn, UK
4Jean MH van den Elsen, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK.
5Richard H ffrench-Constant, Centre for Ecology and Conservation, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK.

Tóm tắt

AbstractBACKGROUND: Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450–substrate interactions.RESULTS: Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X‐ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also ‘V’‐shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT–CYP6G1 complex and a non‐resistant CYP6A2 homology model implies that tight‐fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin.CONCLUSION: The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities. Copyright © 2010 Society of Chemical Industry

Từ khóa


Tài liệu tham khảo

10.1016/B0-44-451924-6/00049-1

10.1016/S0965-1748(99)00038-7

10.1016/S0378-1119(03)00763-7

10.1073/pnas.86.5.1465

10.1073/pnas.0503709102

10.1016/S0378-1119(03)00725-X

10.1111/j.1432-1033.2004.04025.x

10.1098/rstb.1998.0321

10.1146/annurev.ento.44.1.507

10.1016/S0378-1119(00)00533-3

10.1126/science.1074170

10.1007/s004380100531

10.1016/j.ibmb.2007.02.008

10.1002/ps.1472

10.1534/genetics.106.066597

10.1111/j.1365-294X.2004.02263.x

10.1016/S0965-1748(03)00064-X

10.1073/pnas.0303793101

10.1016/j.cub.2005.07.054

10.1046/j.1365-2583.2002.00344.x

10.1016/S0965-1748(96)00036-7

10.1073/pnas.89.11.4855

10.1023/B:GENE.0000019920.71944.2b

10.1093/protein/gzl012

10.1021/jm040180d

RobertsonJL RussellRMandSavinNE POLO: a user's guide to probit or logit analysis. United States Department of Agriculture Forestry Service General Technical Report PSW‐38 (1980).

10.1111/j.1574-6941.2006.00060.x

10.1074/jbc.C400293200

10.1093/protein/gzg075

10.1107/S0021889892009944

10.1126/science.1099736

10.1186/gb-2000-1-6-reviews3003

10.1016/S0021-9258(18)48462-1

10.1016/j.tibs.2004.11.004

10.1016/j.jinorgbio.2004.02.007

10.1073/pnas.2336095100

10.1073/pnas.0603236103

10.1038/295601a0

Larkin GJ, 2000, Fate and effects of diazinon, Rev Environ Contam Toxicol, 166, 49

Pronk ME, 2000, Toxicological Evaluation of Certain Veterinary Drug Residues in Food, 75

10.1002/(SICI)1099-0461(1999)13:1<53::AID-JBT7>3.0.CO;2-2

10.1021/tx0600696

10.1042/BST0341252

10.1016/j.ibmb.2008.03.008

10.1016/j.ibmb.2009.08.006

10.1111/j.1365-2583.2005.00532.x

10.1038/nbt744

10.1074/jbc.M500158200

10.1093/protein/gzi023

10.1093/molbev/msl118

10.1002/arch.940280403

10.1289/ehp.9087255

10.1016/0048-3575(81)90033-X

10.1073/pnas.0709249105

Thông tin
Thông tin xuất bản

Pest Management Science

Tập 66 Số 10

1106-1115

Thông tin tác giả