Productive Structure

DNMT 1 Productive Structure

Formation of productive DNMT1-DNA complex involves the infiltration of both the major groove by two TRD loops and the minor groove by the catalytic loop, causing large helical distortion.

The side chain of Met 1235 from the catalytic loop inserts into the DNA from the minor groove and occupies the space vacated by the extruded fC7’ on the target strand.The target cytosine that is  looped out of the helix and into the active site(fC7'), where it is methylated due to proximity to AdoMet (S-adenosylhomocysteine (AdoHcy)

The side chain of Lys 1537 from TRD loop 2 inserts into the DNA from the major groove an occupies empty space on the parental strand, which results from translation of the stacked orphan guanine(G7) by one step along the DNA helix toward the 3’end, also flip out the downstream residue C8.

TRD loops 1&2 insert and span both strands on the major grooves centered about the hemi-CpG. TRD 1 contacts the phosphate backbone of the parental strand. TRD 2 involved in base-specific recognition of the hemi-mCpG step and the DNA cavity. Both have contribution to recognize the 5 methy group of mC6, participate in the formation of concave surface.

The orphan Guanine G7(complementary with the extruded fC7') form non-cononical  base pair with G8 in the parental strand.