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刚果锥虫丙酮酸激酶的结构与动力学特征

Structural and kinetic characterization of Trypanosoma congolense pyruvate kinase.

作者信息

Pinto Torres Joar Esteban, Yuan Meng, Goossens Julie, Versées Wim, Caljon Guy, Michels Paul A, Walkinshaw Malcolm D, Magez Stefan, Sterckx Yann G-J

机构信息

Research Unit for Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.

Centre for Translational and Chemical Biology, School of Biological Sciences, The University of Edinburgh, Michael Swann Building, The King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, United Kingdom.

出版信息

Mol Biochem Parasitol. 2020 Mar;236:111263. doi: 10.1016/j.molbiopara.2020.111263. Epub 2020 Feb 19.

Abstract

Trypanosoma are blood-borne parasites and are the causative agents of neglected tropical diseases (NTDs) affecting both humans and animals. These parasites mainly rely on glycolysis for their energy production within the mammalian host, which is why trypanosomal glycolytic enzymes have been pursued as interesting targets for the development of trypanocidal drugs. The structure-function relationships of pyruvate kinases (PYKs) from trypanosomatids (Trypanosoma and Leishmania) have been well-studied within this context. In this paper, we describe the structural and enzymatic characterization of PYK from T. congolense (TcoPYK), the main causative agent of Animal African Trypanosomosis (AAT), by employing a combination of enzymatic assays, thermal unfolding studies and X-ray crystallography.

摘要

锥虫是通过血液传播的寄生虫,是影响人类和动物的被忽视热带病(NTDs)的病原体。这些寄生虫在哺乳动物宿主体内主要依靠糖酵解来产生能量,这就是为什么锥虫糖酵解酶一直是开发杀锥虫药物的有趣靶点。在这种背景下,对来自锥虫(锥虫属和利什曼原虫属)的丙酮酸激酶(PYK)的结构-功能关系进行了充分研究。在本文中,我们通过结合酶活性测定、热变性研究和X射线晶体学,描述了来自刚果锥虫(TcoPYK)的PYK的结构和酶学特征,刚果锥虫是动物非洲锥虫病(AAT)的主要病原体。

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