Structural domains comprising this superfamily share the structure of the catalytic domain of some type IIP restriction endonucleases such as BcnI and MVal. BcnI cleaves duplex DNA containing the sequence CC/SGG, where S is G or C, and MvaI cleaves the sequence CC/WGG, where W is an A or a T nucleotide. Bot generate staggered products with single nucleotide 5prime-overhangs. Both enzymes bind duplex DNA in 1:1 stoichiometric ratio.

Structural studies have shown that both Mval and BcnI show a two-lobe architecture. According to their function the two lobes have been termed catalytic lobe and recognition lobe, as the former contains all active site residues and the latter is involved in sequence recognition. The catalytic lobe also contributes some of the minor grove interactions with DNA, which are unlikely to play a major role in sequence discrimination PMID:17344322,PMID:17445830.