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

Sotnichenko, S. E.; Mikhailov, A. M.

doi:10.1134/S1063774513020156

Title: 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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Abstract

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 {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} 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 diffractionmore »« less

Authors:

Sotnichenko, S. E.; Mikhailov, A. M. ^[1]

Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

Publication Date:: Fri Mar 15 00:00:00 EDT 2013

OSTI Identifier:: 22156320

Resource Type:: Journal Article

Journal Name:: Crystallography Reports

Additional Journal Information:: Journal Volume: 58; Journal Issue: 2; Other Information: Copyright (c) 2013 Pleiades Publishing, Ltd.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 1063-7745

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; 36 MATERIALS SCIENCE; ESCHERICHIA COLI; GASTROINTESTINAL TRACT; INFECTIOUS DISEASES; LAYERS; LIGANDS; MONOMERS; PHOSPHATES; PROTEINS; PROTOZOA; SALMONELLA TYPHIMURIUM; SYNTHESIS; URIDINE; X-RAY DIFFRACTION

Citation Formats


                    Lashkov, A. A., E-mail: alashkov83@gmail.com, Sotnichenko, S. E., and Mikhailov, A. M. 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.  United States: N. p., 2013. 
        Web.  doi:10.1134/S1063774513020156.

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                    Lashkov, A. A., E-mail: alashkov83@gmail.com, Sotnichenko, S. E., & Mikhailov, A. M. 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.  United States.  https://doi.org/10.1134/S1063774513020156

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                    Lashkov, A. A., E-mail: alashkov83@gmail.com, Sotnichenko, S. E., and Mikhailov, A. M. 2013.  
        "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".  United States.  https://doi.org/10.1134/S1063774513020156.

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@article{osti_22156320,

  title        = {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},

  author       = {Lashkov, A. A., E-mail: alashkov83@gmail.com and Sotnichenko, S. E. and Mikhailov, A. M.},

  abstractNote = {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 {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} 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).},

  doi          = {10.1134/S1063774513020156},

  url          = {https://www.osti.gov/biblio/22156320},
  journal      = {Crystallography Reports},

  issn         = {1063-7745},

  number       = 2,

  volume       = 58,

  place        = {United States},

  year         = {Fri Mar 15 00:00:00 EDT 2013},

  month        = {Fri Mar 15 00:00:00 EDT 2013}

}

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