Fig. 4.

I119 disrupts tertiary contacts within the SAM-binding site. SAM interacts with residues in β1 (I52), β2 (T57, S59), α3 (H64), β3 (S86), α4 (S88), β4 (D109, H110), α5 (L114), β5 (D141), α6 (R143), β9 (V213) and α8 (Q221). The orientations of SAM-binding residues in β1, β2, β5, α6 and α8 become more disordered in the 119I PIMT simulations, opening up the active site. In the 119V apoprotein simulations, the SAM-binding site remains similar to that of the holoprotein crystal structure. This lack of movement may restrict binding and release of SAM. Side chains of SAM-binding residues from the final ns of three independent simulations of the 119V and 119I PIMT apoproteins are overlaid. SAH from the 119V PIMT crystal structure (1I1N) is included to show how the residues are oriented relative to the co-product. A color version of this figure is available as supplementary data at PEDS online.