Mechanism and Evolution of DNA Recognition by DNA-(adenine N6)-Methyltransferases from the EcoDam Family
Albert Jeltsch and Tomasz P. Jurkowski
Structural and functional studies have illustrated how the T4Dam DNA‑(adenine N6)‑methyltransferase recognizes its GATC target sites, showing that the TC part of the target sequence is contacted by a b‑hairpin loop formed by an amino acid motif conserved in the Dam family of DNA MTases. Besides T4Dam, experimental data on DNA recognition specificity of members from this family are available for EcoDam, M.FokI and M.EcoRV, all supporting an important role for this conserved element in DNA recognition. Biochemical analysis of sequence‑specific DNA recognition by these proteins shed light on the evolutionary pathways that led to changes in their sequence specificity. Despite their similarity there are interesting differences in the mechanism of DNA recognition among members of the EcoDam family which illustrate some general processes of molecular evolution that have shaped protein‑DNA recognition. a) the recognition of the first guanine is done by a lysine residue located in an N‑terminal loop in EcoDam and M.EcoRV and by an arginine from the b‑hairpin in T4Dam; and b) M.EcoRV bends its target site and, therefore, recognizes the GATATC sequence as an expanded GATC site. Finally, the conformational transitions during substrate recognition by T4Dam, EcoDam and M.EcoRV are discussed in this review.