Residues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs

Authors

• Bo Lin, Hainan Medical CollegeFollow
• Shi-Hua Xiang, University of Nebraska-LincolnFollow
• Mengsen Li, Hainan Medical College

Document Type

Article

Date of this Version

2016

Citation

Mar. Drugs 2016, 14, 173; doi:10.3390/md14100173

Comments

This document is published under a Creative Commons/Open Access license.

Abstract

Nicotinic acetylcholine receptors (nAChRs) are targets for developing new drugs to treat severe pain, nicotine addiction, Alzheimer disease, epilepsy, etc. α-Conotoxins are biologically and chemically diverse. With 12–19 residues and two disulfides, they can be specifically selected for different nAChRs. Acetylcholine-binding proteins from Aplysia californica (Ac-AChBP) are homologous to the ligand-binding domains of nAChRs and pharmacologically similar. X-ray structures of the α-conotoxin in complex with Ac-AChBP in addition to computer modeling have helped to determine the binding site of the important residues of α-conotoxin and its affinity for nAChR subtypes. Here, we present the various α-conotoxin residues that are selective for Ac-AChBP or nAChRs by comparing the structures of α-conotoxins in complex with Ac-AChBP and by modeling α-conotoxins in complex with nAChRs. The knowledge of these binding sites will assist in the discovery and design of more potent and selective α-conotoxins as drug leads.