Jia L G, Shimokawa K, Bjarnason J B, Fox J W
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Toxicon. 1996 Nov-Dec;34(11-12):1269-76. doi: 10.1016/s0041-0101(96)00108-0.
A large number of zinc metalloproteinases of varying mol. wts and biological functions has been isolated from crotalid and viperid venoms. Over the past few years, structural studies on these proteinases have suggested their organization into four classes, P-I to P-IV. These proteinases are synthesized in the venom gland as zymogens which are subsequently processed to the active form. The signal and pro-sequences of the proteins are highly conserved. Within the pro-domain lies a consensus sequence which probably functions in a manner similar to the cysteine switch in mammalian collagenases. The proteinase domain is represented by two forms: a two-disulfide and a three-disulfide structure. Crystallographic and modeling studies suggest that the two forms share very similar tertiary structures. The larger venom metalloproteinases (P-II, III and IV) have additional domains on the carboxy side of the proteinase domain. The additional domains that have been identified include disintegrin and disintegrin-like domains, a high-cysteine domain and a lectin-binding domain. It appears that these non-enzymatic domains function to modulate the biological properties of the proteinases. Recently, a family of homologues of the venom zinc metalloproteinases has been described from a variety of organisms including mammals, reptiles and invertebrates. This family of proteins has been termed the ADAMs, for A Disintegrin-like And Metalloproteinase-containing protein. They differ from the venom proteinases in that some of them may not have proteolytic activity. In addition to the domain structure described for the P-III class of venom proteins, the ADAMs have an epidermal growth factor-like domain, a transmembrane domain and a cytoplasmic domain. A description of venom metalloproteinase structure will be outlined in this review, along with the similarities and differences among the venom proteins and the ADAMs family of proteins.
已从蝰蛇科和蝮蛇科蛇毒中分离出大量分子量和生物学功能各异的锌金属蛋白酶。在过去几年中，对这些蛋白酶的结构研究表明，它们可分为四类，即P-I至P-IV。这些蛋白酶在毒腺中作为酶原合成，随后被加工成活性形式。蛋白质的信号序列和前序列高度保守。在前结构域内有一个共有序列，其功能可能类似于哺乳动物胶原酶中的半胱氨酸开关。蛋白酶结构域有两种形式：二硫键结构和三硫键结构。晶体学和模型研究表明，这两种形式具有非常相似的三级结构。较大的蛇毒金属蛋白酶（P-II、III和IV）在蛋白酶结构域的羧基侧有额外的结构域。已确定的额外结构域包括解整合素和类解整合素结构域、高半胱氨酸结构域和凝集素结合结构域。看来这些非酶结构域的功能是调节蛋白酶的生物学特性。最近，已从包括哺乳动物、爬行动物和无脊椎动物在内的多种生物体中描述了蛇毒锌金属蛋白酶的一个同源物家族。这个蛋白质家族被称为ADAMs，即含解整合素样和金属蛋白酶的蛋白质。它们与蛇毒蛋白酶的不同之处在于，其中一些可能没有蛋白水解活性。除了为蛇毒蛋白P-III类描述的结构域外，ADAMs还有一个表皮生长因子样结构域、一个跨膜结构域和一个细胞质结构域。本综述将概述蛇毒金属蛋白酶的结构，以及蛇毒蛋白与ADAMs蛋白家族之间的异同。
