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Crystal structure of an insecticide-resistant acetylcholinesterase mutant from the malaria vector Anopheles gambiae in complex with a difluoromethyl ketone inhibitorCrystal structure of an insecticide-resistant acetylcholinesterase mutant from the malaria vector Anopheles gambiae in complex with a difluoromethyl ketone inhibitor
Structural highlights
FunctionACES_ANOGA Rapidly hydrolyzes choline released into the synapse. Publication Abstract from PubMedMalaria is a devastating disease in sub-Saharan Africa and is transmitted by the mosquito Anopheles gambiae. While indoor residual spraying of anticholinesterase insecticides has been useful in controlling the spread of malaria, widespread application of these compounds has led to the rise of an insecticide-resistant mosquito strain that harbors a G119S mutation in the nervous system target enzyme acetylcholinesterase. We demonstrate the atomic basis of insecticide resistance through structure determination of the G119S mutant acetylcholinesterase of An. gambiae in the ligand-free state and bound to a potent difluoromethyl ketone inhibitor. These structures reveal specific features within the active-site gorge distinct from human acetylcholinesterase, including an open channel at the base of the gorge, and provide a means for improving species selectivity in the rational design of improved insecticides for malaria vector control. Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance.,Cheung J, Mahmood A, Kalathur R, Liu L, Carlier PR Structure. 2018 Jan 2;26(1):130-136.e2. doi: 10.1016/j.str.2017.11.021. Epub 2017, Dec 21. PMID:29276037[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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