Identification of an ITPase/XTPase in Escherichia coli by structural and biochemical analysis

Structure. 2005 Oct;13(10):1511-20. doi: 10.1016/j.str.2005.07.007.

Abstract

Inosine triphosphate (ITP) and xanthosine triphosphate (XTP) are formed upon deamination of ATP and GTP as a result of exposure to chemical mutagens and oxidative damage. Nucleic acid synthesis requires safeguard mechanisms to minimize undesired lethal incorporation of ITP and XTP. Here, we present the crystal structure of YjjX, a protein of hitherto unknown function. The three-dimensional fold of YjjX is similar to those of Mj0226 from Methanococcus janschii, which possesses nucleotidase activity, and of Maf from Bacillus subtilis, which can bind nucleotides. Biochemical analyses of YjjX revealed it to exhibit specific phosphatase activity for inosine and xanthosine triphosphates and have a possible interaction with elongation factor Tu. The enzymatic activity of YjjX as an inosine/xanthosine triphosphatase provides evidence for a plausible protection mechanism by clearing the noncanonical nucleotides from the cell during oxidative stress in E. coli.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate* / metabolism
  • Antigens, Neoplasm / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Crystallography, X-Ray
  • Dimerization
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Guanosine Triphosphate / metabolism
  • Inosine Triphosphatase
  • Inosine Triphosphate / chemistry
  • Kinetics
  • Methanococcus / enzymology
  • Methanococcus / genetics
  • Mitochondrial Proteins
  • Models, Molecular
  • Peptide Elongation Factor Tu / metabolism
  • Peptide Mapping
  • Protein Folding
  • Protein Structure, Secondary
  • Pyrophosphatases / chemistry*
  • Ribonucleotides / chemistry
  • Spectrum Analysis, Raman
  • Static Electricity
  • Structure-Activity Relationship
  • Sulfates / chemistry
  • Sulfates / metabolism

Substances

  • Antigens, Neoplasm
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Maf protein, Bacillus subtilis
  • Mitochondrial Proteins
  • Ribonucleotides
  • Sulfates
  • TUFM protein, human
  • Inosine Triphosphate
  • xanthosine 5'-triphosphate
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Peptide Elongation Factor Tu
  • Pyrophosphatases
  • YjjX protein, E coli