The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor function
The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor function
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DOI：
10.1073/pnas.0403072101
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发表时间：
2004-06-15
影响因子：
11.1
通讯作者：
Everse, SJ
中科院分区：
文献类型：
--
作者：
Adams, TE;Hockin, MF;Everse, SJ
在脊椎动物止血中，因子Va作为凝血酶原酶复合物中的辅因子，与单独的因子Xa相比，其导致凝血酶生成速率增加300，000倍。在结构上，很少有人知道的机制，其中因子Va改变催化在这个复杂的。在这里，我们报告的晶体结构的蛋白C失活因子Va（A1（.）A3-C1-C2），其描绘了先前未表征的结构域排列。这种取向对与功能所必需的膜结合有影响。一个高亲和力的钙结合位点和铜结合位点都已被确定。令人惊讶的是，两者都没有直接参与连锁联想。这种结构代表迄今为止解决的最大的生理相关片段因子Va，并为未来一代凝血辅因子模型提供了新的支架。
In vertebrate hemostasis, factor Va serves as the cofactor in the prothrombinase complex that results in a 300,000-fold increase in the rate of thrombin generation compared with factor Xa alone. Structurally, little is known about the mechanism by which factor Va alters catalysis within this complex. Here, we report a crystal structure of protein C inactivated factor Va (A1(.)A3-C1-C2) that depicts a previously uncharacterized domain arrangement. This orientation has implications for binding to membranes essential for function. A high-affinity calcium-binding site and a copper-binding site have both been identified. Surprisingly, neither shows a direct involvement in chain association. This structure represents the largest physiologically relevant fragment of factor Va solved to date and provides a new scaffold for the future generation of models of coagulation cofactors.