Snake venom metalloproteinases: Structure, function and relationship to the Adams family of proteins
Snake venom metalloproteinases: Structure, function and relationship to the Adams family of proteins
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DOI：
10.1016/s0041-0101(96)00108-0
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发表时间：
1996-11-01
期刊：
影响因子：
2.8
通讯作者：
Fox, JW
中科院分区：
文献类型：
--
作者：
Jia, LG;Shimokawa, KI;Fox, JW
锌金属蛋白水解酶的数量变化不一。已从鳄鱼和蛇毒中分离出具有WTS和生物学功能的毒素。在过去的几年里，对这些酶的结构研究表明，它们的组织结构分为四个类别，P-I到P-IV。这些蛋白酶在毒腺中以酵素的形式合成，随后被加工成活性形式。蛋白质的信号和前体序列是高度保守的。在原结构域中有一个共同的序列，其功能可能类似于哺乳动物胶原酶中的半胱氨酸开关。蛋白水解酶结构域有两种形式：二二硫键和三二硫键结构。结晶学和模型研究表明，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一侧有额外的结构域。已确定的其他结构域包括去整合素和去整合素样域，一个高半胱氨酸域和一个凝集素结合域。似乎这些非酶结构域的作用是调节蛋白水解酶的生物学特性。最近，从哺乳动物、爬行动物和无脊椎动物等多种生物中描述了毒液锌金属蛋白酶的同源物家族。这个蛋白质家族被称为ADAMS，意为去整合素样蛋白和含有金属蛋白酶的蛋白。它们与蛇毒蛋白水解酶的不同之处在于，它们中的一些可能不具有蛋白分解活性。除了P-III类毒蛋白的结构域结构外，ADAMS还具有表皮生长因子样结构域、跨膜结构域和细胞质结构域。本文将对蛇毒金属蛋白酶的结构进行概述，并对其与Adams家族蛋白的异同作一综述。版权所有(C)1996爱思唯尔科学有限公司
A large number of zinc metalloproteinases of varying mel. 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. Copyright (C) 1996 Elsevier Science Ltd