Comparison of Protein Structures Reveals Monophyletic Origin of
the AdoMet-Dependent Methyltransferase Family and Mechanistic Convergence
Rather than Recent Differentiation of N4-Cytosine and N6-Adenine DNA
Methylation
Affiliations: Molecular Biology Research Program, Henry Ford Health
System, Detroit, MI, USA
Note: [] Correspondence to: J.M. Bujnicki, Molecular Biology Research
Program, Henry Ford Health System, One Ford Place, Suite 5D Detroit, MI 48202,
USA. Tel: +1 313 874 6128; Fax: +1 313 876 2380; E-mail:
[email protected] or: [email protected]
Abstract: Phylogenetic analysis of the S-adenosyl-L-methionine-dependent
methyltransferases was performed based on similarity of positions of main chain
á-carbon atoms in published structures of members of this
superfamily. The evolutionary tree was inferred and the problem of
mono/polyphyletic origin of DNA methyltransferases from the Rossmann-fold
enzymes was solved, bridging two seemingly antithetical
hypotheses. The comparison of protein structures provides evidence
for an evolutionary link between widely diverged subfamilies of RNA and DNA
N6-adenine methyltransferases and argues against the close homology of
N6-adenine and N4-cytosine methyltransferases, apparent from biochemical data
and comparison of fragments of sequences. Such evolutionary analysis
of methyltransferases has never been published yet in the literature and will
guide further phylogenetical studies based on both sequence and structure
comparison.
