Structure and other chemical characterizations of gila toxin, a lethal toxin from lizard venom.
The complete primary structure of a lethal toxin, horridum toxin, from the venom of the lizard, Heloderma horridum horridum, was determined by Edman degradation. The amino acid sequence was deduced by overlapping peptide fragments generated by chemical and enzymatic digestions. Horridum toxin causes hemorrhage in internal organs and particularly in the eye, leading to exophthalmia, an effect that has not been observed for other toxins. It is a glycoprotein with a total of 210 residues. Examination of the primary sequence revealed that horridum toxin has considerable homology to tissue-type kallikrein and trypsin. Furthermore, synthetic substrates for trypsin, such as tosyl-L-arginine methyl ester, benzoyl-L-arginine ethyl ester and other p-nitroanilide substrates, were hydrolyzed. The toxin released bradykinin upon hydrolysis of kininogen. This enzymatic behavior is similar to that of plasma kallikrein: however, the presence of a characteristic "kallikrein-like" loop at 91-100 (GTIYNCNYVN) in the primary structure and other features similar to tissue kallikrein suggest that horridum toxin is more like tissue kallikrein. This toxin degraded all three chains of fibrinogen but did not form a clot, which suggests that it is different from thrombin. Moreover, it differs from another lethal factor from H. horridum horridum, gila toxin, which has 245 amino acid residues and does not cause exophthalmia.
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Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D002241:Carbohydrates / Q000032:analysis; D002845:Chromatography; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D005094:Exophthalmos / Q000139:chemically induced; D008401:Gas Chromatography-Mass Spectrometry; D006023:Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced; D006867:Hydrolases; D007610:Kallikreins / Q000737:chemistry; D008116:Lizards; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014688:Venoms / Q000737:chemistry*
D002241:Carbohydrates; D006023:Glycoproteins; D010455:Peptides; D014688:Venoms; C031673:gilatoxin; D006867:Hydrolases; C110275:horridum toxin, Heloderma horridum; D007610:Kallikreins