Fig. 5.

The V119I polymorphism affects salt-bridge networks near the substrate-binding interface. Structures from the 119V PIMT simulations closely resemble the crystal structure. The V119I mutation increases the mobility of the α2-β1 loop, β1 and β2, leading to a slight rotation in α3 that promotes the formation of a salt bridge between D73 (α3) and R177 (β8) at the bottom of the substrate-binding interface. This salt bridge allows the iosapartate-binding surface to open up as contacts between residues in α3 (M63, L70) and β9 (Y212, L207) are lost. The V119I mutation also disrupts the R143-D217 salt bridge, allowing α8 to move away from the SAM-binding site. Structures from the final ns of three independent simulations of 119V and 119I PIMT are overlaid and colored from blue (N-terminus) to red (C-terminus). Side chains are shown in stick representation and colored by atom type. Residue 119 is on the opposite face of the protein from the isoaspartate-binding site and is not visible in this orientation. A color version of this figure is available as supplementary data at PEDS online.