6ARY

Crystal structure of an insecticide-resistant acetylcholinesterase mutant from the malaria vector Anopheles gambiae in complex with a difluoromethyl ketone inhibitor

6ARY の概要

• エントリーDOI: 10.2210/pdb6ary/pdb
• 分子名称: Acetylcholinesterase, (1S)-2,2-difluoro-1-[1-(pentan-3-yl)-1H-pyrazol-4-yl]ethan-1-ol, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: hydrolase, difluoromethyl ketone, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Anopheles gambiae (African malaria mosquito)
• 細胞内の位置: Cell junction, synapse: Q869C3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123187.96

構造登録者

Cheung, J.,Mahmood, A.,Kalathur, R.,Lixuan, L.,Carlier, P.R. (登録日: 2017-08-23, 公開日: 2018-01-10, 最終更新日: 2024-10-16)

主引用文献

Cheung, J.,Mahmood, A.,Kalathur, R.,Liu, L.,Carlier, P.R.
Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance.
Structure, 26:130-136.e2, 2018

PubMed Abstract: Malaria 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.

PubMed: 29276037
DOI: 10.1016/j.str.2017.11.021

実験手法

X-RAY DIFFRACTION (2.257 Å)