7PDR

Crystal structure of Lymnaea stagnalis Acetylcholine-binding protein (Ls-AChBP) Q55R/M114V double mutant complexed with Dichloromezotiaz

This is a non-PDB format compatible entry.

Summary for 7PDR

• Entry DOI: 10.2210/pdb7pdr/pdb
• Descriptor: Acetylcholine-binding protein, 3-[3,5-bis(chloranyl)phenyl]-1-[(2-chloranyl-1,3-thiazol-5-yl)methyl]-9-methyl-pyrido[1,2-a]pyrimidine-2,4-dione (3 entities in total)
• Functional Keywords: acetylcholine, protein, insecticide, signaling protein
• Biological source: Lymnaea stagnalis (Great pond snail, Helix stagnalis)
• Total number of polymer chains: 5
• Total formula weight: 121355.85

Authors

Montgomery, M.G. (deposition date: 2021-08-06, release date: 2022-02-02, Last modification date: 2024-10-16)

Primary citation

Montgomery, M.,Rendine, S.,Zimmer, C.T.,Elias, J.,Schaetzer, J.,Pitterna, T.,Benfatti, F.,Skaljac, M.,Bigot, A.
Structural Biology-Guided Design, Synthesis, and Biological Evaluation of Novel Insect Nicotinic Acetylcholine Receptor Orthosteric Modulators.
J.Med.Chem., 65:2297-2312, 2022

PubMed Abstract: The development of novel and safe insecticides remains an important need for a growing world population to protect crops and animal and human health. New chemotypes modulating the insect nicotinic acetylcholine receptors have been recently brought to the agricultural market, yet with limited understanding of their molecular interactions at their target receptor. Herein, we disclose the first crystal structures of these insecticides, namely, sulfoxaflor, flupyradifurone, triflumezopyrim, flupyrimin, and the experimental compound, dicloromezotiaz, in a double-mutated acetylcholine-binding protein which mimics the insect-ion-channel orthosteric site. Enabled by these findings, we discovered novel pharmacophores with a related mode of action, and we describe herein their design, synthesis, and biological evaluation.

PubMed: 34986308
DOI: 10.1021/acs.jmedchem.1c01767

Experimental method

X-RAY DIFFRACTION (2.33 Å)