Molecular Determinants Conferring the Stoichiometric-Dependent Activity of α-Conotoxins at the Human α9α10 Nicotinic Acetylcholine Receptor Subtype

Authors

Rilei Yu, Qingdao National Laboratory for Marine Science and Technology, Ocean University of China
Han-Shen Tae, University of Wollongong
Nargis Tabassum, Ocean University of China, Qingdao National Laboratory for Marine Science and Technology
Juan Shi, Ocean University of China, Qingdao National Laboratory for Marine Science and Technology
Tao Jiang, Qingdao National Laboratory for Marine Science and Technology, Ocean University of China
David J. Adams, University of WollongongFollow

RIS ID

128183

Publication Details

Yu, R., Tae, H., Tabassum, N., Shi, J., Jiang, T. & Adams, D. J. (2018). Molecular Determinants Conferring the Stoichiometric-Dependent Activity of α-Conotoxins at the Human α9α10 Nicotinic Acetylcholine Receptor Subtype. Journal of Medicinal Chemistry, 61 (10), 4628-4634.

Abstract

α9α10 nicotinic acetylcholine receptors (nAChRs) putatively exist at different stoichiometries. We systematically investigated the molecular determinants of α-conotoxins Vc1.1, RgIA#, and PeIA inhibition at hypothetical stoichiometries of the human α9α10 nAChR. Our results suggest that only Vc1.1 exhibits stoichiometric-dependent inhibition at the α9α10 nAChR. The hydrogen bond between N154 of α9 and D11 of Vc1.1 at the α9(+)-α9(−) interface is responsible for the stoichiometric dependent potency of Vc1.1.

Grant Number

ARC/DP150103990