Characterization of nicked myotoxin a and its effect on the sarcoplasmic reticulum calcium pump.
Myotoxin a, a muscle-necrotizing polypeptide isolated from Crotalus viridis viridis (prairie rattlesnake) venom, was nicked at Met-28 by cyanogen bromide. Amino acid analysis indicated that the methionine content was reduced to zero from the original 1 mol. Judging from circular dichroism, the nicked myotoxin a had a conformation similar to that of original myotoxin. Raman spectra indicated that the conformations of the three disulfide bonds are not affected in nicked myotoxin a. Like the original toxin, nicked myotoxin a was myotoxic and inhibited calcium ion loading activity, although the inhibitory action was slightly lower than that of the original myotoxin a. Both modified and unmodified myotoxin a showed myonecrotic activity as determined by examining histological slides. The modified toxin also inhibited the formation of decavanadate-induced two-dimensional crystalline arrays of the sarcoplasmic reticulum Ca2+-ATPase just as the original myotoxin a does.
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Department of Biochemistry, Colorado State University, Fort Collins 80523.
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002942:Circular Dichroism; D003435:Crotalid Venoms / Q000494:pharmacology*; D003461:Crystallography; D003488:Cyanogen Bromide; D066298:In Vitro Techniques; D015394:Molecular Structure; D009132:Muscles / Q000187:drug effects / Q000473:pathology*; D009336:Necrosis; D010446:Peptide Fragments; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship
D003435:Crotalid Venoms; D010446:Peptide Fragments; C018932:myotoxin A; D000252:Calcium-Transporting ATPases; D003488:Cyanogen Bromide; D002118:Calcium