Fig. 5.

Crosstalk mechanisms. (A, Left) An optimal OGT substrate motif predicts a Ser/Thr near the P0 O-GlcNAc site. Phosphorylation at P−3 hampers O-GlcNAcylation. (Right) A structural basis for this observation can be postulated, looking at the OGT active site (gray surface) with UDP (white sticks) and the CK2 peptide substrate (green sticks) bound (PDB ID code 4GYY). CK2 residues are labeled with respect to the O-GlcNAcylation site. The small pocket size at P−3 suggests that the incorporation of a phosphate moiety here is sterically hindered. For clarity, the TPR domain on OGT is omitted. (B) Reciprocal crosstalk between phosphorylation/O-GlcNAcylation is not likely on Pro-directed phosphorylation sites.