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New insights on repellent recognition by Anopheles gambiae odorant-binding protein 1

Tzotzos, George; Iley, Jim N. and Moore, Elaine A. (2018). New insights on repellent recognition by Anopheles gambiae odorant-binding protein 1. PLoS ONE, 13(4), article no. e0194724.

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It is generally recognized that insect odorant binding proteins (OBPs) mediate the solubilisation and transport of hydrophobic odorant molecules and contribute to the sensitivity of the insect olfactory system. However, the exact mechanism by which OBPs deliver odorants to olfactory receptors and their role, if any, as selectivity filters for specific odorants, are still a matter of debate. In the case of Anopheles gambiae recent studies indicate that ligand discrimination is effected through the formation of heterodimers such as AgamOBP1 and AgamOBP4 (odorant binding proteins 1 and 4 from Anopheles gambiae). Furthermore, AgamOBPs have been reported to be promiscuous in binding more than one ligand simultaneously and repellents such as DEET (N,N-diethyl-3-toluamide) and 6-MH (6-methyl-5-hepten-2-one) interact directly with mosquito OBPs and/or compete for the binding of attractive odorants thus disrupting OBP heterodimerisation. In this paper, we propose mechanisms of action of DEET and 6-MH. We also predict that ligand binding can occur in several locations of AgamOBP1 with partial occupancies and propose structural features appropriate for repellent pharmacophores.

Item Type: Journal Item
Copyright Holders: 2018 The Authors
ISSN: 1932-6203
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Other Departments > Other Departments
Other Departments
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Research Group: Health and Wellbeing PRA (Priority Research Area)
Item ID: 54036
Depositing User: Elaine Moore
Date Deposited: 04 Apr 2018 11:11
Last Modified: 01 May 2019 18:05
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