3C84

Crystal structure of a complex of AChBP from aplysia californica and the neonicotinoid thiacloprid

Summary for 3C84

• Entry DOI: 10.2210/pdb3c84/pdb
• Related: 3C79
• Descriptor: Soluble acetylcholine receptor, {(2Z)-3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide, ISOPROPYL ALCOHOL, ... (5 entities in total)
• Functional Keywords: acetylcholine binding protein, neonicotinoid, receptor, choline-binding protein
• Biological source: Aplysia californica (California sea hare)
• Total number of polymer chains: 5
• Total formula weight: 130743.89

Authors

Talley, T.T.,Harel, M.,Hibbs, R.E.,Tomizawa, M.,Casida, J.E.,Taylor, P.W. (deposition date: 2008-02-08, release date: 2008-05-20, Last modification date: 2023-08-30)

Primary citation

Talley, T.T.,Harel, M.,Hibbs, R.E.,Radic, Z.,Tomizawa, M.,Casida, J.E.,Taylor, P.
Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore.
Proc.Natl.Acad.Sci.Usa, 105:7606-7611, 2008

PubMed Abstract: Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 A in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids.

PubMed: 18477694
DOI: 10.1073/pnas.0802197105

Experimental method

X-RAY DIFFRACTION (1.94 Å)