title: Residues Responsible for the Selectivity of α-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. 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 fromAplysia 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.
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, Hainan, China. linbo_752@163.com.|Institution of Tumor, Hainan Medical College, Haikou 570102, Hainan, China. linbo_752@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Nebraska Center for Virology, School of Veterinary Medicine and Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. sxiang2@unl.edu.
authors.forename: Shihua
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, Hainan, China. mengsenli@163.com.|Institution of Tumor, Hainan Medical College, Haikou 570102, Hainan, China. mengsenli@163.com.
authors.forename: Mengsen
authors.initials: M
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D020916:Conotoxins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D009792:Oceans and Seas; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020916:Conotoxins; D011978:Receptors, Nicotinic; D000109:Acetylcholine
keywords: Ac-AChBP; X-ray structure; design; model; nAChRs; α-conotoxins