title: Selective disulfide formation in truncated apamin and sarafotoxin.
abstract: Apamin and sarafotoxin are small peptide toxins which are 18 and 21 residues long, respectively. They both have cysteines at positions 1, 3, 11, and 15. However, the non-cysteine portions of their sequences and the positions of their disulfides are different. In native apamin, the cysteines form disulfides 1-11 and 3-15, whereas in sarafotoxin they form the 1-15 and 3-11 pairs. Truncated analogs have been synthesized which lack the carboxyl-terminal tails following cysteine-15. When oxidized by glutathione, both truncated sequences retain the ability to selectively populate the disulfide combination observed in the respective full-length parent. This ability is retained in the presence of the denaturing agent 5 M guanidinium chloride. Circular dichroism spectra of the nativelike isomers are nearly identical to those of the parent sequence, and are not affected by heating to 75 degrees C or exposure to 5 M guanidinium chloride. The alpha helix observed in apamin is a consequence of both the disulfide topology and the non-cysteine portions of the sequence. There is not much alpha helix when apamin is forced to adopt the disulfides found in native sarafotoxin or when sarafotoxin is forced to adopt the disulfides found in native apamin.
authors.affiliation: Department of Biological Sciences, State University of New York, Buffalo 14260.
authors.forename: K
authors.initials: K
authors.lastname: Ramalingam
authors.forename: G H
authors.initials: GH
authors.lastname: Snyder
mesh_terms: D000595:Amino Acid Sequence; D001030:Apamin / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D004220:Disulfides / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D006358:Hot Temperature; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D014757:Viper Venoms / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004220:Disulfides; D006146:Guanidines; D014757:Viper Venoms; C057354:sarafotoxins s6; D001030:Apamin; D005978:Glutathione; D019791:Guanidine