Structure-guided analysis reveals nine sequence motifs conserved among DNA amino-methyltransferases, and suggests a catalytic mechanism for these enzymes

J Mol Biol. 1995 Nov 3;253(4):618-32. doi: 10.1006/jmbi.1995.0577.


Previous X-ray crystallographic studies have revealed that the catalytic domain of a DNA methyltransferase (Mtase) generating C5-methylcytosine bears a striking structural similarity to that of a Mtase generating N6-methyladenine. Guided by this common structure, we performed a multiple sequence alignment of 42 amino-Mtases (N6-adenine and N4-cytosine). This comparison revealed nine conserved motifs, corresponding to the motifs I to VIII and X previously defined in C5-cytosine Mtases. The amino and C5-cytosine Mtases thus appear to be more closely related than has been appreciated. The amino Mtases could be divided into three groups, based on the sequential order of motifs, and this variation in order may explain why only two motifs were previously recognized in the amino Mtases. The Mtases grouped in this way show several other group-specific properties, including differences in amino acid sequence, molecular mass and DNA sequence specificity. Surprisingly, the N4-cytosine and N6-adenine Mtases do not form separate groups. These results have implications for the catalytic mechanisms, evolution and diversification of this family of enzymes. Furthermore, a comparative analysis of the S-adenosyl-L-methionine and adenine/cytosine binding pockets suggests that, structurally and functionally, they are remarkably similar to one another.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence*
  • Cytosine / metabolism
  • Evolution, Molecular
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • S-Adenosylmethionine
  • Sequence Alignment


  • S-Adenosylmethionine
  • Cytosine
  • Methyltransferases

Associated data

  • GENBANK/P05103
  • SWISSPROT/P00473
  • SWISSPROT/P00475
  • SWISSPROT/P04043
  • SWISSPROT/P04392
  • SWISSPROT/P04393
  • SWISSPROT/P09358
  • SWISSPROT/P14230
  • SWISSPROT/P14243
  • SWISSPROT/P14244
  • SWISSPROT/P14751
  • SWISSPROT/P14827
  • SWISSPROT/P14871
  • SWISSPROT/P18051
  • SWISSPROT/P20590
  • SWISSPROT/P23192
  • SWISSPROT/P23941
  • SWISSPROT/P24582
  • SWISSPROT/P25201
  • SWISSPROT/P25238
  • SWISSPROT/P29347
  • SWISSPROT/P29538
  • SWISSPROT/P29568
  • SWISSPROT/P30774
  • SWISSPROT/P31118
  • SWISSPROT/P34720
  • SWISSPROT/P34721
  • SWISSPROT/Q01511
  • SWISSPROT/Q04845