Preparation and Structure of a New Coagulation Factor XI Catalytic Domain for Drug Discovery
Preparation and Structure of a New Coagulation Factor XI Catalytic Domain for Drug Discovery
复制标题
用于药物发现的新型凝血因子 XI 催化结构域的制备和结构
DOI：
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发表时间：
2011
影响因子：
2.2
通讯作者：
Jiang, Longguang
中科院分区：
文献类型：
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作者：
Zhao, BaoYu;Yuan, Cai;Zhang, Xu;Huang, Mingdong;Wang, Yu;Chen, Hongwei;Jiang, Longguang
人凝血因子XI(FXIa)是凝血级联反应放大阶段的关键酶，近年来被认为是抗凝血剂开发的重要靶点。我们设计了一种新的FXIa催化域突变体rFXI370~607(N73Q-N113Q-C123S)，并报道了该蛋白的制备、蛋白结晶和晶体结构。在序列和结构水平上与胰酶家族丝氨酸蛋白酶进行比较后，我们突出了FXIa的几个独特的结构特征，为开发新的效力和特异性更高的小分子FXIa抑制剂奠定了基础。
Human blood coagulation factor XI (FXI) is a key enzyme in the amplification phase of blood coagulation cascade,and is recognized as an important target for anti-coagulant deve-lopment in recent years.We designed a new mutant form of FXIa catalytic domain rhFXI 370～607 (N73Q-N113Q-C123S),and report here the facile preparation,protein crystallization,and crystal structure of this protein.We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels.This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.