Figure 3.

Putative 3D models to explain the glycosylation of T³ and S¹⁴ of MUC1^4TR catalyzed by GalNAc-T2. (A) 3D view of complex GalNAc-T2/1 derived from a representative frame obtained from 0.5 μs of MD simulation. A key CH−π interaction between the β-methyl group of T³ and the aromatic ring of F372 is shown in dashed lines (distance 4.8 ± 0.4 Å). (B) 3D view of the binding site of GalNAc-T2/2 derived from a representative frame obtained from 0.5 μs of MD simulation. A relevant hydrogen bond, 38% populated through the whole trajectory, between the GalNAc at T⁶ of 2 (T¹⁵ in MUC1^4TR) and W265 is highlighted in dashed lines. In both structures, the catalytic domain is displayed in orange and the lectin domain is depicted in green. In the glycopeptides, the GalNAc units are shown in yellow sticks. UDP-GalNAc is displayed in gray sticks and Mn²⁺ is shown as a cyan sphere. Relevant residues of the glycopeptides and some residues of catalytic domain are also shown as sticks and in a different color. Schematic representation of the sequential glycosylation process at T³ and S¹⁴ of MUC1^4TR catalyzed by GalNAc-T2 is also displayed. These models highlight the N-terminal preference of GalNAc-T2.