Dimerisation-dependent GTPase reaction of MnmE: how potassium acts as GTPase-activating element

EMBO J. 2006 Jun 21;25(12):2940-51. doi: 10.1038/sj.emboj.7601171. Epub 2006 Jun 8.


MnmE, a Guanine nucleotide-binding protein conserved between bacteria and man, is involved in the modification of tRNAs. Here we provide biochemical and X-ray structural evidence for a new GTP-hydrolysis mechanism, where the G-domains of MnmE dimerise in a potassium-dependent manner and induce GTP hydrolysis. The structure in the presence of GDP-AlFx and potassium shows how juxtaposition of the subunits induces a conformational change around the nucleotide which reorients the catalytic machinery. A critical glutamate is positioned such as to stabilise or activate the attacking water. Potassium provides a positive charge into the catalytic site in a position analogous to the arginine finger in the Ras-RasGAP system. Mutational studies show that potassium-dependent dimerisation and GTP hydrolysis can be uncoupled and that interaction between the G-domains is a prerequisite for subsequent phosphoryl transfer. We propose a model for the juxtaposition of G-domains in the full-length protein and how it induces conformational changes in the putative tRNA-modification centre.

MeSH terms

  • Aluminum Compounds / metabolism
  • Amino Acid Sequence
  • Binding Sites / genetics
  • Catalysis
  • Crystallography, X-Ray
  • Dimerization
  • Enzyme Activation / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Fluorides / metabolism
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Nucleotides / metabolism
  • Potassium / metabolism
  • Potassium / pharmacology*
  • Protein Binding
  • Protein Structure, Quaternary


  • Aluminum Compounds
  • Escherichia coli Proteins
  • Nucleotides
  • GTP Phosphohydrolases
  • MnmE protein, E coli
  • Fluorides
  • Potassium
  • aluminum fluoride