Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Acta Crystallogr D Struct Biol. 2024 Aug 1;80(Pt 8):629-638. doi: 10.1107/S2059798324006594. Epub 2024 Jul 25.
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It bears a significant global health burden with limited treatment options, thus calling for the development of new and effective drugs. Certain trypanosomal metabolic enzymes have been suggested to be druggable and valid for subsequent inhibition. In this study, the crystal structure of glycerol kinase from T. cruzi, a key enzyme in glycerol metabolism in this parasite, is presented. Structural analysis allowed a detailed description of the glycerol binding pocket, while comparative assessment pinpointed a potential regulatory site which may serve as a target for selective inhibition. These findings advance the understanding of glycerol metabolism in eukaryotes and provide a solid basis for the future treatment of Chagas disease.
恰加斯病是一种由原生动物寄生虫克氏锥虫引起的被忽视的热带病。它给全球健康带来了巨大的负担,治疗选择有限,因此需要开发新的有效药物。某些锥虫代谢酶已被认为具有成药性,并可随后进行抑制。在这项研究中,展示了克氏锥虫甘油激酶的晶体结构,甘油激酶是该寄生虫中甘油代谢的关键酶。结构分析可以详细描述甘油结合口袋,而比较评估则确定了一个潜在的调节位点,该位点可能成为选择性抑制的靶标。这些发现增进了对真核生物甘油代谢的理解,并为未来治疗恰加斯病提供了坚实的基础。