Characterization of the mutX gene of Streptococcus pneumoniae as a homologue of Escherichia coli mutT, and tentative definition of a catalytic domain of the dGTP pyrophosphohydrolases

Mol Microbiol. 1994 Jan;11(2):323-30. doi: 10.1111/j.1365-2958.1994.tb00312.x.


We show that deletion of a gene of Streptococcus pneumoniae, which we call mutX, confers a mutator phenotype to resistance to streptomycin. Analysis of the DNA sequence changes that occurred in several streptomycin-resistant mutants showed that mutations are unidirectional AT to CG transversions. The mutX gene is located immediately downstream of the previously identified ung gene and genetic evidence suggests that the two genes are co-ordinately regulated. Nucleotide sequence determination reveals that the mutX gene encodes a 17,870 Da protein (154 residues) which exhibits significant homology with the MutT protein of Escherichia coli, a nucleoside triphosphatase (dGTP pyrophosphohydrolase). The mutX gene complements the E. coli mutT mutator phenotype when introduced on a plasmid. Site-directed mutagenesis and analysis of nitrosoguanidine-induced mutT mutants suggest that a small region of high homology between the two proteins (61% identity over 23 residues) is part of the catalytic site of the nucleoside triphosphatase. Computer searching for sequence homology to MutX uncovered a second E. coli protein, the product of orf17, a gene of unknown function located near the ruvC gene. The region of high homology between MutX and MutT is also conserved in this protein, which raises the interesting possibility that the orf17 gene plays some role in determining mutation rates in E. coli. Finally, a small set of proteins, including a family of virus-encoded proteins and two evolutionarily conserved proteins encoded by an antisense transcript from the Xenopus laevis and human bFGF genes, were also found to harbour significant homology to this highly conserved region.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics*
  • Base Sequence
  • Biological Evolution
  • Conserved Sequence
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Drug Resistance, Microbial / genetics
  • Escherichia coli / genetics*
  • Escherichia coli Proteins*
  • Genes, Bacterial*
  • Genetic Complementation Test
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Phosphoric Monoester Hydrolases / biosynthesis
  • Phosphoric Monoester Hydrolases / genetics*
  • Pyrophosphatases
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / enzymology*
  • Streptococcus pneumoniae / genetics*
  • Streptomycin / toxicity


  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Oligodeoxyribonucleotides
  • MutX protein, Streptococcus pneumoniae
  • Phosphoric Monoester Hydrolases
  • Pyrophosphatases
  • mutT protein, E coli
  • Streptomycin

Associated data

  • GENBANK/Z21702