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粘帚霉甘油醛-3-磷酸脱氢酶与醛糖酸复合物的结构。

Structure of glyceraldehyde-3-phosphate dehydrogenase from Paracoccidioides lutzii in complex with an aldonic sugar acid.

机构信息

Department of Chemistry, State University of Ponta Grossa, Ponta Grossa, PR, 84030-900, Brazil.

Federal Institute of Paraná-Campus Irati, Irati, PR, 84507-302, Brazil.

出版信息

Biochimie. 2024 Mar;218:20-33. doi: 10.1016/j.biochi.2023.09.013. Epub 2023 Sep 12.

DOI:10.1016/j.biochi.2023.09.013
PMID:37709188
Abstract

The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north regions of the latter. It belongs to the Ajellomycetaceae family, Onygenales order, and is typically thermodimorphic, presenting yeast cells when it grows in animal tissues, but mycelia when in the environment, where it produces the infectious propagule. This fungus is one of the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic fungal infection in Latin America. Investigations on its genome have contributed to a better understanding about its metabolism and revealed the complexity of several metabolic glycolytic pathways. Glyceraldehyde-3-Phosphate Dehydrogenase from Paracoccidioides lutzii (PlGAPDH) is considered a moonlighting protein and participates in several biological processes of this pathogen. The enzyme was expressed and purified, as seen in SDS-PAGE gel, crystallized and had its three dimensional structure (3D) determined in complex with NAD, a sulphate ion and d-galactonic acid, therefore, a type of 'GAA site'. It is the first GAPDH structure to show this chemical type in this site and how this protein can bind an acid derived from oxidation of a linear hexose.

摘要

巴西耳霉(Pb01)病原体存在于南美洲的哥伦比亚、厄瓜多尔、委内瑞拉和巴西,特别是在后者的中部、西部和北部地区。它属于子囊菌门、球腔菌目,通常为温度双相型,在动物组织中生长时呈酵母细胞状,在环境中则呈菌丝状,并在此处产生感染性繁殖体。这种真菌是原虫性球孢子菌病(PCM)的病原体之一,是拉丁美洲最重要的地方性真菌感染。对其基因组的研究有助于更好地了解其代谢,并揭示了几种糖酵解途径的复杂性。巴西耳霉中的甘油醛-3-磷酸脱氢酶(PlGAPDH)被认为是一种多功能蛋白,参与该病原体的几个生物学过程。该酶在 SDS-PAGE 凝胶中显示表达和纯化,结晶并确定了其与 NAD、硫酸根离子和 D-半乳糖酸复合物的三维结构(3D),因此是一种“GAA 位点”。这是第一个显示该化学类型的 GAPDH 结构,以及这种蛋白质如何结合由线性己糖氧化产生的酸。

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