Datta G, Tu A T
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA.
J Pept Res. 1997 Dec;50(6):443-50. doi: 10.1111/j.1399-3011.1997.tb01207.x.
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.
通过埃德曼降解法确定了来自墨西哥毒蜥毒液中的一种致死毒素——恐怖毒素的完整一级结构。通过化学和酶促消化产生的重叠肽片段推导氨基酸序列。恐怖毒素会导致内脏出血，尤其是眼部出血，进而导致眼球突出，这种效应在其他毒素中尚未观察到。它是一种共有210个残基的糖蛋白。对一级序列的研究表明，恐怖毒素与组织型激肽释放酶和胰蛋白酶具有相当高的同源性。此外，胰蛋白酶的合成底物，如甲苯磺酰-L-精氨酸甲酯、苯甲酰-L-精氨酸乙酯和其他对硝基苯胺底物，都能被水解。该毒素在激肽原水解时释放缓激肽。这种酶促行为与血浆激肽释放酶相似：然而，在一级结构中91-100位存在特征性的“类激肽释放酶”环（GTIYNCNYVN）以及其他与组织激肽释放酶相似的特征表明，恐怖毒素更像组织激肽释放酶。这种毒素能降解纤维蛋白原的所有三条链，但不会形成凝块，这表明它与凝血酶不同。此外，它与来自墨西哥毒蜥的另一种致死因子——吉拉毒素不同，吉拉毒素有245个氨基酸残基，不会导致眼球突出。
