InterPro: IPR002296 N6 adenine-specific DNA methyltransferase, N12 class

In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. There are 2 major classes of DNA methyltransferase that differ in the nature of the modifications they effect. The members of one class (C-MTases) methylate a ring carbon and form C5-methylcytosine (see IPR001525). Members of the second class (N-MTases) methylate exocyclic nitrogens and form either N4-methylcytosine (N4-MTases) or N6-methyladenine (N6-MTases). Both classes of MTase utilise the cofactor S-adenosyl-L-methionine (SAM) as the methyl donor and are active as monomeric enzymes [1].

N-6 adenine-specific DNA methylases (EC:2.1.1.72) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA. Such enzymes are found in the three existing types of bacterial restriction-modification systems (in type I system the A-Mtase is the product of the hsdM gene, and in type III it is the product of the mod gene). All of these enzymes recognise a specific sequence in DNA and methylate an adenine in that sequence. It has been shown [2, 3, 4, 5] that A-Mtases contain a conserved motif Asp/Asn-Pro-Pro-Tyr/Phe in their N-terminal section, this conserved region could be involved in substrate binding or in the catalytic activity. The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A [6]. The molecule folds into 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded beta-sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small beta-sheets and 8 alpha-helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate. A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements [5]. According to this classification, N6-MTases that have an NPPY motif (CM II) occuring after the FxGxG motif (CM I) are designated N12 class N6-adenine MTases.