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

ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) are targets for developing new drugs to treat severe pain, nicotine addiction, Alzheimer disease, epilepsy, etc. ?-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 ?-conotoxin in complex with Ac-AChBP in addition to computer modeling have helped to determine the binding site of the important residues of ?-conotoxin and its affinity for nAChR subtypes. Here, we present the various ?-conotoxin residues that are selective for Ac-AChBP or nAChRs by comparing the structures of ?-conotoxins in complex with Ac-AChBP and by modeling ?-conotoxins in complex with nAChRs. The knowledge of these binding sites will assist in the discovery and design of more potent and selective ?-conotoxins as drug leads.

SUBMITTER: Lin B

PROVIDER: S-EPMC5082321 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Lin Bo B Xiang Shihua S Li Mengsen M

Marine drugs 20161011 10

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 <i>Aplysia californica</i> (Ac-AChBP) are homologous to the ligand-binding domains of nAChRs and pharmacologically similar. X-ray structures of the α-conotoxi ...[more]

PMID: 27727162

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