title: Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels.
abstract: A new peptide antagonist of voltage-activated calcium channels was purified from venom of the funnel web spider, Agelenopsis aperta. This 48-amino acid peptide, omega-agatoxin (omega-Aga)-IVB, was found to be a potent (Kd, approximately 3 nM) blocker of P-type calcium channels in rat cerebellar Purkinje neurons but had no activity against T-type, L-type, or N-type calcium channels in a variety of neurons. The calcium channel-blocking properties of omega-Aga-IVB were similar to those of another toxin, omega-Aga-IVA, which has 71% amino acid identity with omega-Aga-IVB. The 10-fold greater abundance of omega-Aga-IVB in venom allowed structural studies using NMR spectroscopy. The three-dimensional structure derived from NMR data resulted in a proposed disulfide bond configuration for the peptide. Although omega-Aga-IVB has fewer basic and more acidic residues than does omega-Aga-IVA, the two toxins show conservation of positively charged residues in a mid-peptide region that is predicted to form one face of the omega-Aga-IVB molecule. This region may be crucial for high affinity binding to the P-type calcium channel. In contrast, the amino termini of the two toxins have different charges and seem unlikely to be involved in binding to the channel.
authors.affiliation: Department of Entomology, University of California, Riverside 92521.
authors.forename: M E
authors.initials: ME
authors.lastname: Adams
authors.forename: I M
authors.initials: IM
authors.lastname: Mintz
authors.forename: M D
authors.initials: MD
authors.lastname: Reily
authors.forename: V
authors.initials: V
authors.lastname: Thanabal
authors.forename: B P
authors.initials: BP
authors.lastname: Bean
mesh_terms: D060848:Agatoxins; D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000648:ultrastructure; D020867:omega-Agatoxin IVA
chemical_list: D060848:Agatoxins; D002121:Calcium Channel Blockers; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; C083855:omega-agatoxin-Aa4b