Department of Pharmaceutical Sciences, Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, Novara, Italy.
Department of Bacteriology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, Japan.
PLoS One. 2017 Apr 18;12(4):e0175815. doi: 10.1371/journal.pone.0175815. eCollection 2017.
Mycobacterium smegmatis represents one model for studying the biology of its pathogenic relative Mycobacterium tuberculosis. The structural characterization of a M. tuberculosis ortholog protein can serve as a valid tool for the development of molecules active against the M. tuberculosis target. In this context, we report the biochemical and structural characterization of M. smegmatis phosphoribosylpyrophosphate synthetase (PrsA), the ortholog of M. tuberculosis PrsA, the unique enzyme responsible for the synthesis of phosphoribosylpyrophosphate (PRPP). PRPP is a key metabolite involved in several biosynthetic pathways including those for histidine, tryptophan, nucleotides and decaprenylphosphoryl-arabinose, an essential precursor for the mycobacterial cell wall biosynthesis. Since M. tuberculosis PrsA has been validated as a drug target for the development of antitubercular agents, the data presented here will add to the knowledge of the mycobacterial enzyme and could contribute to the development of M. tuberculosis PrsA inhibitors of potential pharmacological interest.
耻垢分枝杆菌是研究其致病性相关分枝杆菌结核分枝杆菌生物学的模型之一。结核分枝杆菌同源蛋白的结构特征可以作为开发针对结核分枝杆菌靶标的活性分子的有效工具。在这种情况下，我们报告了分枝杆菌磷酸核糖焦磷酸合成酶（PrsA）的生化和结构特征，PrsA 是结核分枝杆菌 PrsA 的同源物，是唯一负责合成磷酸核糖焦磷酸（PRPP）的酶。PRPP 是一种关键代谢物，参与包括组氨酸、色氨酸、核苷酸和脱磷酸化阿拉伯糖在内的几种生物合成途径，是分枝杆菌细胞壁生物合成的必需前体。由于结核分枝杆菌 PrsA 已被验证为开发抗结核药物的药物靶点，因此这里提供的数据将有助于了解分枝杆菌酶，并可能有助于开发具有潜在药理意义的结核分枝杆菌 PrsA 抑制剂。
