6ARX
Crystal structure of an insecticide-resistant acetylcholinesterase mutant from the malaria vector Anopheles gambiae in the ligand-free state
Summary for 6ARX
| Entry DOI | 10.2210/pdb6arx/pdb |
| Descriptor | Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose, CITRATE ANION, ... (5 entities in total) |
| Functional Keywords | hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Anopheles gambiae (African malaria mosquito) |
| Cellular location | Cell junction, synapse: Q869C3 |
| Total number of polymer chains | 2 |
| Total formula weight | 122691.41 |
| Authors | Cheung, J.,Mahmood, A.,Kalathur, R.,Lixuan, L.,Carlier, P.R. (deposition date: 2017-08-23, release date: 2018-01-10, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 29276037DOI: 10.1016/j.str.2017.11.021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.302 Å) |
Structure validation
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