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https://hdl.handle.net/2440/116058
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Type: | Journal article |
Title: | Recognition and detoxification of the insecticide DDT by Drosophila melanogaster glutathione S-transferase D1 |
Author: | Low, W.Y. Feil, S.C. Ng, H.L. Gorman, M.A. Morton, C.J. Pyke, J. McConville, M.J. Bieri, M. Mok, Y.F. Robin, C. Gooley, P.R. Parker, M.W. Batterham, P. |
Citation: | Journal of Molecular Biology, 2010; 399(3):358-366 |
Publisher: | Academic Press Ltd- Elsevier Science Ltd |
Issue Date: | 2010 |
ISSN: | 0022-2836 1089-8638 |
Statement of Responsibility: | Wai Yee Low, Susanne C. Feil, Hooi Ling Ng, Michael A. Gorman, Craig J. Morton, James Pyke, Malcolm J. McConville, Michael Bieri, Yee-Foong Mok, Charles Robin, Paul R. Gooley, Michael W. Parker and Philip Batterham |
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 A 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 orientation favoring catalysis. Two-dimensional (1)H,(15)N heteronuclear single-quantum coherence NMR experiments of GSTD1 indicate that conformational changes occur upon glutathione and DDT binding and the residues that broaden upon DDT binding support the predicted binding site. We also show that the ancestral GSTD1 is likely to have possessed DDT dehydrochlorinase activity because both GSTD1 from D. melanogaster and its sibling species, Drosophila simulans, have this activity. |
Keywords: | Glutathione S-transferase DDT Insecticide NMR |
Rights: | © 2010 Elsevier Ltd. All rights reserved. |
DOI: | 10.1016/j.jmb.2010.04.020 |
Published version: | http://dx.doi.org/10.1016/j.jmb.2010.04.020 |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 3 |
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