Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X
Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X
复制标题
DOI：
10.1073/pnas.131179698
复制
发表时间：
2001-06-19
影响因子：
11.1
通讯作者：
Morita, T
中科院分区：
文献类型：
--
作者：
Mizuno, H;Fujimoto, Z;Morita, T
血凝因子的γ -羧谷氨酸（Gla）结构域负责Ca2+依赖性磷脂膜结合。因子X结合蛋白（Factor X-binding protein, X-bp）是一种来自蛇毒的抗凝蛋白，它能特异性结合到因子X的cia结构域。在2.3埃分辨率下，X-bp与因子X的Gla结构域肽形成复合物的晶体结构表明，其抗凝作用是基于复合物形成中隐藏了两个对膜结合至关重要的cia结构域。因此，Gla结构域有望成为抗凝药物的新靶点，而X-bp为抗凝药物的设计提供了依据。这种结构也提供了因子X的膜结合模型。
The gamma -carboxyglutamic acid (Gla) domain of blood coagulation factors is responsible for Ca2+-dependent phospholipid membrane binding. Factor X-binding protein (X-bp), an anticoagulant protein from snake venom, specifically binds to the cia domain of factor X. The crystal structure of X-bp in complex with the Gla domain peptide of factor X at 2.3-Angstrom resolution showed that the anticoagulation is based on the fact that two patches of the cia domain essential for membrane binding are buried in the complex formation. The Gla domain thus is expected to be a new target of anticoagulant drugs, and X-bp provides a basis for designing them. This structure also provides a membrane-bound model of factor X.