CXXC domain in mDNMT1 adopts a crescent like fold similar to that adopted by the MLL1 CXXC domain:
There are 2 coordinated zinc ions (shown as spheres below) with 8 Cys residues that are positioned within two helical segments (clearly shown below, Cys residues adjacent to the alpha helix interacting with the Zn ion in coordinated complex):
The image clearly shows the CXXC domain interacting with the major and minor grooves of the DNA. This interaction occurs over a 4bp footprint, the major groove is penetrated by a Arg-Ser-Lys-Gln loop segment which forms base specific phosphodiester bonds:
Lys(686) and Gln(687) of the CXXC domain interacts with the guanine bases by side chain interactions, and the cytosine bases are recognised by backbone interactions with Ser(685) and Lys(686). There is also various salt bridges between arginine side chains and the phosphodiester backbone of the DNA.
The paper also confirmed reports about the domain specifically binding to unmethylated CpG dinucleotides (M. D. Allen et al 2006, M. Birke et al 2002), the stuctural data confirms that 'methylation of either cytosine in the CpG step would create severe steric clashes with peptide atoms'.
In brief this means that if the DNMT1 enzyme bound to a methylated CpG dinucleotide it would be highly unfavorable due to steric clashes and therefore very unlikely to happen.
