The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B

Aaron J. Oakley, Thasaneeya Harnnoi, Rungrutai Udomsinprasert, Kanya Jirajaroenrat, Albert J. Ketterman, Matthew C.J. Wilce

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Abstract

Glutathione S-transferases (GSTs) are dimeric proteins that play an important role in cellular detoxification. Four GSTs from the mosquito Anopheles dirus species B (Ad), an important malaria vector in South East Asia, are produced by alternate splicing of a single transcription product and were previously shown to have detoxifying activity towards pesticides such as DDT. We have determined the crystal structures for two of these alternatively spliced proteins, AdGST1-3 (complexed with glutathione) and AdGST1-4 (apo form), at 1.75 and 2.45 Å resolution, respectively. These GST isozymes show differences from the related GST from the Australian sheep blowfly Lucilia cuprina; in particular, the presence of a C-terminal helix forming part of the active site. This helix causes the active site of the Anopheles GSTs to be enclosed. The glutathione-binding helix α2 and flanking residues are disordered in the AdGST1-4 (apo) structure, yet ordered in the AdGST1-3 (GSH-bound) structure, suggesting that insect GSTs operate with an induced fit mechanism similar to that found in the plant phi- and human pi-class GSTs. Despite the high overall sequence identities, the active site residues of AdGST1-4 and AdGST1-3 have different conformations.

Original languageEnglish
Pages (from-to)2176-2185
Number of pages10
JournalProtein Science
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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    Oakley, A. J., Harnnoi, T., Udomsinprasert, R., Jirajaroenrat, K., Ketterman, A. J., & Wilce, M. C. J. (2001). The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B. Protein Science, 10(11), 2176-2185. https://doi.org/10.1110/ps.21201