Recognition and detoxification of the insecticide DDT by drosophila melanogaster glutathione S-transferase D1

WY Low; SC Feil; HL Ng; MA Gorman; CJ Morton; J Pyke; MJ McConville; M Bieri; YF Mok; C Robin; PR Gooley; MW Parker; P Batterham

Journal article

Recognition and detoxification of the insecticide DDT by drosophila melanogaster glutathione S-transferase D1

WY Low, SC Feil, HL Ng, MA Gorman, CJ Morton, J Pyke, MJ McConville, M Bieri, YF Mok, C Robin, PR Gooley, MW Parker, P Batterham

Journal of Molecular Biology | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2010

DOI: 10.1016/j.jmb.2010.04.020

Abstract

GSTD1 is one of several insect glutathione S-transferases capable of metabolizing the insecticide DDT. Here we use crystallography and NMR to elucidate the binding of DDT and glutathione to GSTD1. The crystal structure of Drosophila melanogaster GSTD1 has been determined to 1.1 Å resolution, which reveals that the enzyme adopts the canonical GST fold but with a partially occluded active site caused by the packing of a C-terminal helix against one wall of the binding site for substrates. This helix would need to unwind or be displaced to enable catalysis. When the C-terminal helix is removed from the model of the crystal structure, DDT can be computationally docked into the active site in an ..

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University of Melbourne Researchers

Michael Gorman Author

Craig Morton Author

Malcolm McConville Author

Yee Foong Mok Author

Related Projects (1)

Using comparative genomics to identify genes responsible for adaptation to environmental toxins

The US National Human Genome Research Institute has committed to sequencing the genomes of ten different Drosophila (fly) species. We will..

Grants

Awarded by U.S. Department of Energy

Funding Acknowledgements

We thank Bio21 for providing isotopes and access to the 800 -MHz NMR spectrometer and Dr. Helen Benes for providing the clone of DmGSTD1. We also thank Harry Tong and other BioCARS staff for their help at the Advanced Photon Source. This work was supported by the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia under the Major National Research Facilities Program. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Energy Research. This work was also supported by grants from the Australian Research Council (ARC) and the Australian Cancer Research Foundation to M.W.P. and an ARC grant (DP0557497) to P.B. and C.R. S.C.F. is a National Health and Medical Research Council of Australia (NHMRC) Industry Fellow and M.W.P. is an ARC Federation Fellow and NHMRC Honorary Fellow.