Comparative structural analysis of the caspase family with other clan CD cysteine peptidases.
Comparative structural analysis of the caspase family with other clan CD cysteine peptidases.
复制标题
DOI：
10.1042/bj20141324
复制
发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Mottram JC
中科院分区：
文献类型：
--
作者：
McLuskey K;Mottram JC
CD族形成半胱氨酸肽酶的结构群，包含七个单独的家族和两个结构相关酶的亚家族。在历史上，它最著名的是含有哺乳动物的半胱天冬酶，氏族的结构就是在这个基础上建立的。有趣的是，半胱天冬酶家族分为两个亚家族：半胱天冬酶，以及包含副半胱天冬酶和后半胱天冬酶的第二个亚家族。结构数据现在可用于paracaspases和metacaspases，允许对整个caspase家族进行全面的结构分析。此外，相对过多的结构数据最近已成为许多其他家族在氏族，允许的结构和结构功能关系的氏族CD进行充分探讨。本综述比较了caspase亚家族中的酶，并对CD家族中的所有结构家族进行了全面的比较。这揭示了一组具有高度保守的结构元件的结构，这些结构元件为肽酶提供了多种底物特异性和活化机制。它还揭示了保守的结构元件参与底物结合，和潜在的自抑制功能，在整个家族，并确认，后半胱天冬酶的半胱天冬酶（和副半胱天冬酶）的结构不同，这表明他们应该形成一个独特的家族CD肽酶。
Clan CD forms a structural group of cysteine peptidases, containing seven individual families and two subfamilies of structurally related enzymes. Historically, it is most notable for containing the mammalian caspases, on which the structures of the clan were founded. Interestingly, the caspase family is split into two subfamilies: the caspases, and a second subfamily containing both the paracaspases and the metacaspases. Structural data are now available for both the paracaspases and the metacaspases, allowing a comprehensive structural analysis of the entire caspase family. In addition, a relative plethora of structural data has recently become available for many of the other families in the clan, allowing both the structures and the structure–function relationships of clan CD to be fully explored. The present review compares the enzymes in the caspase subfamilies with each other, together with a comprehensive comparison of all the structural families in clan CD. This reveals a diverse group of structures with highly conserved structural elements that provide the peptidases with a variety of substrate specificities and activation mechanisms. It also reveals conserved structural elements involved in substrate binding, and potential autoinhibitory functions, throughout the clan, and confirms that the metacaspases are structurally diverse from the caspases (and paracaspases), suggesting that they should form a distinct family of clan CD peptidases.