ω-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer.
A peptide with neurotoxic effect on mammals, purified from the venom of the spider Phoneutria nigriventer, was studied regarding its primary structure and its effects on voltage-gated calcium channels. The peptide, named ω-phonetoxin-IIA, has 76 amino acids residues, with 14 Cys forming 7 disulphide bonds, and a molecular weight of 8362.7 Da. The neurotoxicity is a consequence of the peptide’s blocking effects on high-voltage-activated (HVA) calcium channels. N-type HVA calcium channels of rat dorsal root ganglion neurons are blocked with affinity in the sub-nanomolar concentration range. The toxin also blocks L-type channels of rat β pancreatic cells, with an affinity 40 times lower. Although not studied in detail, evidence indicates that the toxin also blocks other types of HVA calcium channels, such as P and Q. No effect was observed on low-voltage-activated, T-type calcium channels. The significant homologies between ω-phonetoxin-IIA and the peptides of the ω-agatoxin-III family, and the overlapping inhibitory effects on calcium channels are discussed in terms of the structure-activity relationship.
Cassola
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AC
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes, 1524, São Paulo, SP-05508-900, Brazil.
Jaffe
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H
Fales
H M
HM
Afeche
S C
SC
Magnoli
F
F
Cipolla-Neto
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment; D013111:Spider Venoms / Q000737:chemistry* / Q000235:genetics; D013112:Spiders / Q000737:chemistry*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; C558708:omega-phonetoxin-IIA, Phoneutria nigriventer; D002118:Calcium