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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >The Kazal-type inhibitors infestins 1 and 4 differ in specificity but are similar in three-dimensional structure
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The Kazal-type inhibitors infestins 1 and 4 differ in specificity but are similar in three-dimensional structure

机译：Kazal-type抑制剂infestins 1和4是不同的在特异性,但很相似三维结构

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摘要

Blood coagulation is an important process in haemostasis, and disorders of blood coagulation can lead to an increased risk of haemorrhage and thrombosis. Coagulation is highly conserved in mammals and has been comprehensively studied in humans in the investigation of bleeding or thrombotic diseases. Some substances can act as inhibitors of blood coagulation and may affect one or multiple enzymes throughout the process. A specific thrombin inhibitor called infestin has been isolated from the midgut of the haematophagous insect Triatoma infestans. Infestin is a member of the nonclassical Kazal-type serine protease inhibitors and is composed of four domains, all of which have a short central -helix and a small antiparallel β - sheet. Domains 1 and 4 of infestin (infestins 1 and 4) possess specific inhibitory activities. Infestin 1 inhibits thrombin, while infestin 4 is an inhibitor of factor XIIa, plasmin and factor Xa. Here, the structure determination and structural analysis of infestin 1 complexed with trypsin and of infestin 4 alone are reported. Through molecular modelling and docking, it is suggested that the protein-protein binding site is conserved in the infestin 1-thrombin complex compared with other Kazal-type inhibitors. Infestin 4 is able to bind factor XIIa, and the F9N and N11R mutants selected by phage display were shown to be more selective for factor XIIa in comparison to the wild type.
机译：血液凝固是一个重要的过程止血、凝血障碍会导致出血的风险增加和血栓形成。哺乳动物和全面研究人类在出血或调查血栓性疾病。抑制剂的凝血和可能影响在整个过程中一个或多个酶。特定的凝血酶抑制剂叫infestin被隔离的中肠haematophagous昆虫Triatoma 5种。Infestin模的一员Kazal-type丝氨酸蛋白酶抑制剂,由四个领域,所有这些有一个短中央螺旋和一个小反平行的β-床单和4)拥有特定的抑制活性。Infestin 1抑制凝血酶,而Infestin 4XIIa抑制剂的因素,血纤维蛋白溶酶和因子Xa。结构分析infestin 1包裹着胰蛋白酶和infestin 4单独报告。通过分子模拟和对接,它是表明蛋白质结合位点守恒的infestin 1-thrombin复杂吗相对于其他Kazal-type抑制剂。Infestin 4 XIIa能够约束因素,通过噬菌体展示F9N和N11R突变体选择已经被证明更有选择性的因素XIIa吗与野生型相比。

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