A Computer Modeling Study of the Interaction Between Tissue Factor Pathway Inhibitor and Blood Coagulation Factor Xa
A Computer Modeling Study of the Interaction Between Tissue Factor Pathway Inhibitor and Blood Coagulation Factor Xa
复制标题
组织因子途径抑制剂与凝血因子Xa相互作用的计算机模型研究
DOI：
10.1023/a:1026318823516
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
H. Umeyama
中科院分区：
文献类型：
--
作者：
T. Yoneda;H. Komooka;H. Umeyama
组织因子途径抑制剂（TFPI）可抑制凝血因子X活化为因子Xa（FXa）。TFPI的第二Kunitz型抑制结构域（K2）结合FXa的催化结构域，而第一结构域（K1）不结合。我们分析了FXa与K1或K2的复合物的计算机模型，这些复合物是使用FXa的晶体结构制成的。在FXa与K2的复合物中观察到有利的疏水相互作用。此外，我们使用CHIMERA构建了FXa的三级结构，以评估同源性建模方法的准确性。FXa的分离模型结构与晶体结构一致，但对该结构与K1或K2的复合物的分析表明，由于与抑制剂相互作用的几个侧链的位置差异，复合物的模型不能提供与K2更大结合能力的明确证据。
Activation of blood coagulation factor X to factor Xa (FXa) is inhibited by tissue factor pathway inhibitor (TFPI). The second Kunitz-type inhibitory domain (K2) of TFPI binds a catalytic domain of FXa, whereas the first domain (K1) does not. We analyzed computer models of complexes of FXa with K1 or K2, which were made using a crystal structure of FXa. Favorable hydrophobic interaction was observed in the complex of FXa with K2. Furthermore, we constructed a tertiary structure of FXa using CHIMERA to assess the accuracy of a homology modeling method. The isolated model structure of FXa agreed well with the crystal structure, but analyses of complexes of this structure with K1 or K2 revealed that the models of complexes could not provide clear evidence of greater binding ability to K2 because of the positional difference of a few side chains interacting with the inhibitor.