Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives.

ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that belong to the superfamily of Cys loop receptors. Valuable insight into the orthosteric ligand binding to nAChRs in recent years has been obtained from the crystal structures of acetylcholine-binding proteins (AChBPs) that share significant sequence homology with the amino-terminal domains of the nAChRs. alpha-Conotoxins, which are isolated from the venom of carnivorous marine snails, selectively inhibit the signaling of neuronal nAChR subtypes. Co-crystal structures of alpha-conotoxins in complex with AChBP show that the side chain of a highly conserved proline residue in these toxins is oriented toward the hydrophobic binding pocket in the AChBP but does not have direct interactions with this pocket. In this stu

SUBMITTER: Armishaw C 

PROVIDER: S-EPMC2666602 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature