InterPro: IPR018117 DNA methylase, C-5 cytosine-specific, active site

C-5 cytosine-specific DNA methylases (EC:2.1.1.73) (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA [1, 2, 3]. Such enzymes are found in the proteins described below.

• As a component of type II restriction-modification systems in prokaryotes and some bacteriophages. Such enzymes recognise a specific DNA sequence where they methylate a cytosine. In doing so, they protect DNA from cleavage by type II restriction enzymes that recognise the same sequence. The sequences of a large number of type II C-5 Mtases are known.
• In vertebrates, there are a number of C-5 Mtases that methylate CpG dinucleotides. The sequence of the mammalian enzyme is known.

C-5 Mtases share a number of short conserved regions. One of the conserved regions contains a conserved Pro-Cys dipeptide in which the cysteine has been shown [4] to be involved in the catalytic mechanism; it appears to form a covalent intermediate with the C6 position of cytosine. The second smaller region is located at the C-terminal extremity in type-II enzymes and is involved in DNA-binding. The structure of HhaI methyltransferase (M.HhaI) has been resolved to 2.5 A [5]: the molecule folds into 2 domains - a larger catalytic domain containing catalytic and cofactor binding sites, and a smaller DNA recognition domain.