Fig. 2: MRK-560 is observed in the PS1-complex, but not PS2.
From: Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560
a Overall cryo-EM structure of the human PS1-complex bound to MRK-560. MRK-560 is shown as orange ball ad sticks. PS1 in the presence of MRK-560 is colored marine (left panel), which is aligned with PS1 in free state (middle panel). The chlorophenyl (CP) group and the difluorobenzyl (DFB) group of MRK-560 insert deeply into the binding cavity. The trifluoromethanesulfonamide (TFMS) group points towards the intracellular side. MRK-560 binding induces formation of two β-strands in PS1 (right panel). b Cryo-EM structures of the human PS2-complex. Left: The structure of PS2 treated with MRK-560 is colored light purple. Middle: The structure of PS2 treated with MRK-560 (PS2M) is nearly identical to that of apo-PS2 (silver). Right: No density corresponding to MRK-560 is observed in the PS2M map (right panel).
