µ-Theraphotoxin Pn3a inhibition of Ca3.3 channels reveals a novel isoform-selective drug binding site.

Low voltage-activated calcium currents are mediated by T-type calcium channels Ca3.1, Ca3.2, and Ca3.

Interactions of the α3β2 Nicotinic Acetylcholine Receptor Interfaces with α-Conotoxin LsIA and its Carboxylated C-terminus Analogue: Molecular Dynamics Simulations.

Notably, α-conotoxins with carboxy-terminal (C-terminal) amidation are inhibitors of the pentameric nicotinic acetylcholine receptors (nAChRs), which are therapeutic targets for neurological diseases and disorders. The (α3)(β2) nAChR subunit arrangement comprises a pair of α3(+)β2(-) and β2(+)α3(-) interfaces, and a β2(+)β2(-) interface. The β2(+)β2(-) interface has been suggested to have higher agonist affinity relative to the α3(+)β2(-) and β2(+)α3(-) interfaces.

Effects of C-Terminal Carboxylation on α-Conotoxin LsIA Interactions with Human α7 Nicotinic Acetylcholine Receptor: Molecular Simulation Studies.

α-Conotoxins selectively bind to nicotinic acetylcholine receptors (nAChRs), which are therapeutic targets due to their important role in signaling transmission in excitable cells. A previous experimental study has demonstrated that carboxylation of the C-terminal of α-conotoxin LsIA reduces its potency to inhibit human α7 nAChR relative to naturally amidated LsIA. However, little is known about the contribution of conformational changes in the receptor and interactions, induced by C-terminal amidation/carboxylation of conotoxins, to selective binding to nAChRs, since most conotoxins and some disulfide-rich peptides from other conotoxin subfamilies possess a naturally amidated C-terminal.