Bjarnason J B, Fox J W
Science Institute, University of Iceland, Reykjavik.
Pharmacol Ther. 1994;62(3):325-72. doi: 10.1016/0163-7258(94)90049-3.
One of the more significant consequences of crotalid envenomation is hemorrhage. Over the past 50 years of investigation, it is clear that the primary factors responsible for hemorrhage are metalloproteinases present in the venom of these snakes. The biochemical basis for their activity is the proteolytic destruction of basement membrane and extracellular matrix surrounding capillaries and small vessels. These proteinase toxins may also interfere with coagulation, thus complementing loss of blood from the vasculature. Structural studies have shown that these proteinases are synthesized as zymogens and are processed at both the amino and carboxy termini to give the mature protein. The variety of hemorrhagic toxins found in snake venoms is due to the presence of structurally related proteins composed of various domains. The type of domains found in each toxin plays an important role in the hemorrhagic potency of the protein. Recently, structural homologs to the venom hemorrhagic metalloproteinases have been identified in several mammalian reproductive systems. The functional significance of the reproductive proteins is not clear, but in light of the presence of similar domains shared with the venom metalloproteinases, their basic biochemical activities may be similar but with very different consequences. This review discusses the history of hemorrhagic toxin research with emphasis on the Crotalus atrox proteinases. The structural similarities observed among the hemorrhagic toxins are outlined, and the structural relationships of the toxins to the mammalian reproductive proteins are described.
响尾蛇毒中毒较为显著的后果之一是出血。在过去50年的研究中，很明显导致出血的主要因素是这些蛇毒液中存在的金属蛋白酶。其活性的生化基础是对毛细血管和小血管周围基底膜及细胞外基质的蛋白水解破坏。这些蛋白酶毒素也可能干扰凝血，从而加剧血管系统的失血。结构研究表明，这些蛋白酶以酶原形式合成，并在氨基和羧基末端进行加工以产生成熟蛋白。蛇毒中发现的多种出血毒素是由于存在由各种结构域组成的结构相关蛋白。每种毒素中发现的结构域类型在蛋白质的出血效力中起重要作用。最近，在几种哺乳动物生殖系统中发现了与毒液出血金属蛋白酶结构同源的蛋白。这些生殖蛋白的功能意义尚不清楚，但鉴于它们与毒液金属蛋白酶共享相似的结构域，其基本生化活性可能相似，但后果却大不相同。本综述讨论了出血毒素研究的历史，重点是墨西哥矛头蝮蛋白酶。概述了出血毒素之间观察到的结构相似性，并描述了毒素与哺乳动物生殖蛋白的结构关系。
