Hite L A, Jia L G, Bjarnason J B, Fox J W
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Arch Biochem Biophys. 1994 Jan;308(1):182-91. doi: 10.1006/abbi.1994.1026.
Presented here are four new cDNA sequences for hemorrhagic metalloproteinases from Crotalus atrox venom, hemorrhagic toxins a, b, c, and d. Comparison of the translated open reading frames to the mature protein sequences gives evidence for post-translational processing at both the amino and carboxyl termini. This comparison is also the basis for a new classification system for these precursors, based on their different sizes. Protein sequences in the zymogen region support the hypothesis of a cysteine-switch type mechanism of maintaining latency. The coordination geometry around the active site zinc ion is discussed. The relationship between these venom metalloproteinases and a family of mammalian reproductive proteins is also supported by these sequences. The cysteine pattern of the carboxyl-terminal domain of the largest proteinase, hemorrhagic toxin a, is compared to other venom proteinases and to the mammalian proteins, showing both striking similarities and subtle differences. It would appear that these hemorrhagic toxins have resulted from deletions and subsequent divergence from a larger ancestor, one they may have shared with the aforementioned mammalian reproductive proteins.
本文展示了来自西部菱斑响尾蛇毒液的四种出血性金属蛋白酶的新cDNA序列，即出血毒素a、b、c和d。将翻译后的开放阅读框与成熟蛋白序列进行比较，结果表明在氨基和羧基末端均存在翻译后加工。这种比较也是基于这些前体不同大小的新分类系统的基础。酶原区域的蛋白质序列支持维持潜伏性的半胱氨酸开关型机制的假说。讨论了活性位点锌离子周围的配位几何结构。这些序列也支持了这些毒液金属蛋白酶与一类哺乳动物生殖蛋白之间的关系。将最大的蛋白酶出血毒素a的羧基末端结构域的半胱氨酸模式与其他毒液蛋白酶和哺乳动物蛋白进行了比较，结果显示出显著的相似性和细微的差异。这些出血毒素似乎是由一个更大的祖先基因缺失并随后发生分化而产生的，它们可能与上述哺乳动物生殖蛋白拥有共同的祖先。
