Figure 3. Dynamics of the binding site region of native and oxidized phenylalanine hydroxylase.

A: Distance between the catalytic iron center and the Cα-atom of Glu141 included in the flexible Tyr138-loop near the active site. Whereas this distance remains mostly stable in the native state PAH_nat over the simulation time (blue), simulation of PAH_ox shows an initial phase of increased loop flexibility that is followed by decrease of that distance indicating a loop movement towards the active site. This finding is confirmed by calculation of the accessible surface area of the iron center (B). After an initial adaption to the perturbation, PAH_ox shows a constantly reduced accessibility of the catalytic iron center compared to PAH_nat. The overall active site volume (C) is similarly reduced over simulation time in PAH_ox compared to PAH_nat, suggesting a reduced enzyme turnover.