Movie S1.

Contact signaling in the active site of mPGES-1. The movie visualizes one possible pathway of contact signaling within the active site of mPGES-1 depicted within the node diagram in Fig. 3A. Initially, the enzyme is shown oriented within a modeled patch of membrane for perspective. The lumen of the endoplasmic reticulum and cellular cytoplasm are, respectively, located in the upper and lower hemispheres (44). The patch of membrane is then removed to show a charge potential surface representation of the homotrimer, with active sites being located by the binding of GSH shown in stick representation with carbon atoms colored in green. A zoomed-in scene of residues involved in contact signaling is represented with the alternate conformations modeled by qFit (smb.slac.stanford.edu/qFitServer/) shown in stick representation and the Cα backbone of the enzyme in cartoon representation colored by monomer. Sequential van der Waals contact signaling identified by the CONTACT algorithm (28) is then shown via atomic radius of respective alternate conformations in translucent green spheres, whose van der Waals overlaps are highlighted in red. The sequential interactions shown are of the residues as follows: Leu-69 → Thr-34 → Cys-68 → Asp-64 → Lys-41 → Arg-40 → Leu-39 → His-53 → K42 → H53 → Asp-49. This result demonstrates how conformational changes in residues involved in GSH binding can ultimately affect conformations of Asp-49, disrupting its interaction with Arg-126 of the opposing monomer and allowing interaction with GSH thiol (shown as a dashed yellow line).