α1-Antichymotrypsin inactivates staphylococcal cysteine protease in cross-class inhibition

► α-1-antichymotrypsin (ACHT) inhibits staphylococcal cysteine protease, ScpA2. ► Inhibition stoichiometry for ACHT:ScpA2 interaction is 2:1. ► ScpA2 attacks one of two adjacent peptide bonds in reactive site loop (RSL) of ACHT. ► The fate of ScpA2 is determined by the choice of the cleavage site in the RSL of ACHT.