In general, inhibitors possessing a Michael acceptor group as a warhead moiety could form an irreversible (covalent) bond with the catalytic cysteine residue in the following manner (Figure 14): First, the cysteine residue undergoes 1,4‐addition at the inhibitor's Michael acceptor group (warhead). Rapid protonation of the α‐carbanion from His‐H+ leads to the covalent bond formation between the warhead of the inhibitor and the cysteine residue.