Structure of an insect delta-class glutathione S-transferase from a DDT-resistant strain of the malaria vector Anopheles gambiae

Chen, L. Q., Hall, P. R., Zhou, X. Y. E., Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173 and Meehan, E. J. (2003) 'Structure of an insect delta-class glutathione S-transferase from a DDT-resistant strain of the malaria vector Anopheles gambiae'. Acta Crystallographica Section D-Biological Crystallography, Vol 59, pp. 2211-2217.

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Abstract

Glutathione S-transferases (GSTs) are a major family of detoxification enzymes which possess a wide range of substrate specificities. Most organisms possess many GSTs belonging to multiple classes. Interest in GSTs in insects is focused on their role in insecticide resistance; many resistant insects have elevated levels of GST activity. In the malaria vector Anopheles gambiae, elevated GST levels are associated with resistance to the organochlorine insecticide DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane]. This mosquito is the source of an insect GST, agGSTd1-6, which metabolizes DDT and is inhibited by a number of pyrethroid insecticides. The crystal structure of agGSTd1-6 in complex with its inhibitor S-hexyl glutathione has been determined and refined at 2.0 Angstrom resolution. The structure adopts a classical GST fold and is similar to those of other insect delta-class GSTs, implying a common conjugation mechanism. A structure-based model for the binding of DDT to agGSTd1-6 reveals two subpockets in the hydrophobic binding site (H-site), each accommodating one planar p-chlorophenyl ring.

Item Type:	Article
Additional Information:	The original version of this article is the electronic one and can be found at: http://scripts.iucr.org/cgi-bin/paper?S0907444903018493
Subjects:	QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department:	Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI):	https://doi.org/10.1107/s0907444903018493
Depositing User:	Ms Julia Martin
Date Deposited:	11 May 2012 08:24
Last Modified:	30 Aug 2019 17:05
URI:	https://archive.lstmed.ac.uk/id/eprint/2511

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