A novel structural class of K+-channel blocking toxin from the scorpion Pandinus imperator.
A novel peptide was purified and characterized from the venom of the scorpion Pandinus imperator. Analysis of its primary structure reveals that it belongs to a new structural class of K+-channel blocking peptide, composed of only 35 amino acids, but cross-linked by four disulphide bridges. It is 40, 43 and 46% identical to noxiustoxin, margatoxin and toxin 1 of Centruroides limpidus respectively. However, it is less similar (26 to 37% identity) to toxins from scorpions of the geni Leiurus, Androctonus and Buthus. The disulphide pairing was determined by sequencing heterodimers produced by mild enzymic hydrolysis. They are formed between Cys-4-Cys-25, Cys-10-Cys-30, Cys-14-Cys-32 and Cys-20-Cys-35. Three-dimensional modelling, using the parameters determined for charybdotoxin, showed that is it possible to accommodate the four disulphide bridges in the same general structure of the other K+-channel blocking peptides. The new peptide (Pil) blocks Shaker B K+ channels reversibly. It also displaces the binding of a known K+-channel blocker, [125I]noxiustoxin, from rat brain synaptosomal membranes with an IC50 of about 10 nM.
Olamendi-Portugal
T
T
Department of Molecular Recognition and Structural Biology, Universidad Nacional Autonoma de Mexico, Cuernavaca, Mexico.
Gómez-Lagunas
F
F
Gurrola
G B
GB
Possani
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels; D018411:Spodoptera; D013574:Synaptosomes / Q000378:metabolism
D004220:Disulfides; D010455:Peptides; C104751:Pi1 toxin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels; C052567:noxiustoxin; D003545:Cysteine