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

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 nA...

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Bibliographic Details
Published in:Marine Drugs
Main Authors: Bo Lin, Shihua Xiang, Mengsen Li
Format: Article
Language:English
Published: MDPI AG 2016-10-01
Subjects:
α-conotoxins
nAChRs
Ac-AChBP
X-ray structure
model
design
Online Access:http://www.mdpi.com/1660-3397/14/10/173
Description
Summary: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.
ISSN:1660-3397

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