Fig. 6
Antagonistic effects of omecamtiv mecarbil (OM) and blebbistatin (BS) on the sequestered state. Schematic representation of the effects of the inhibitor BS and the activator OM. On top: BS occupies a pocket within the motor domain core, close to the active site. Occupation of this pocket by BS allows to stabilize the PPS conformation without any effect on the local compliance of the lever arm required to form the sequestered state. Thus, BS binding is compatible with the IHM and favors the formation of the sequestered state. On the bottom: OM occupies a pocket at the interface between the converter and the N-ter subdomain11. This pocket is expected to decrease the compliance of the converter/ELC interface and constrain the lever arm in a particularly primed position. There is thus a loss in the compliance required to form the sequestered state if OM is bound to the heads of the Myo2 dimer. This explains why OM is incompatible with the formation of the sequestered state
