a, PAR1 (PDB code 3VW7 in purple) with vorapaxar (yellow) bound was superimposed onto PAR2 (in green) with the positions of AZ8838 (in magenta) and AZ3451 (in orange) indicated. b, c, Differences in the helical trajectories of the extracellular and intracellular side are indicated by red arrows. d, The inward movement of TM5 and TM6 places residues Tyr2425.38, Phe2435.39, His3106.58 and Tyr3116.59 into steric clashes with vorapaxar when superimposed onto PAR1. e, The AZ8838 allosteric pocket is also present in PAR1. His1352.64 in PAR2 is replaced by Tyr1622.64 in PAR1 which would clash with AZ8838.