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首页> 外文期刊>Crystallography reports >In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil
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In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

机译：在计算机上分析耶尔森氏菌假结核中尿苷磷酸化酶同二聚体的三维结构，无配体状态且与5-氟尿嘧啶复合

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摘要

Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to α/β proteins, and its topology is a three-layer α/β/α sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% β strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).
机译：假结核是一种急性感染性疾病，其特征是胃肠道病变。通过选择性抑制来自假结核耶尔森氏菌的病原体的尿苷磷酸化酶的活性，可以获得积极的治疗效果。文献中描述了化学治疗剂5-氟尿嘧啶和抗菌药物的组合对致病性原生动物和细菌细胞的协同作用，所述抗菌药物阻止嘧啶碱基的合成。无论是在无配体状态下还是在与药理剂的复合物中，假性耶尔森氏菌（YptUPh）尿苷磷酸化酶的三维结构都是未知的，这阻碍了对YptUPh选择性抑制剂的研究和设计。通过基于同源性的分子模型确定YptUPh的无配体同二聚体的三维结构。 YptUPh分子亚基的三维结构属于α/β蛋白，其拓扑结构是三层α/β/α三明治。 YptUPh分子的亚基单体由38％的螺旋和24％的β链组成。通过分子对接获得了与5-FU复合的YptUPh同型二聚体结构模型。 5-FU在分子活性位点上的位置与其他细菌尿苷磷酸化酶（鼠伤寒沙门氏菌（StUPh）的尿苷磷酸化酶与5-FU，ID的复合物）的X射线衍射结构上的已知数据非常一致。 PDB：4E1V和来自大肠杆菌的尿苷磷酸化酶（EcUPh）与5-FU和1核糖核糖的复合物，ID PDB：1RXC）。

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