(A) The consensus catalytic mechanism of the enzymes from the SH superfamily. (B) Generic structure of an activity-based probe, having three components, i.e. the reactive group or warhead, a linker and a reporter tag. (C) Reaction of a SH enzyme with a fluorophosphonate (FP) activity probe, leading to the formation of an irreversible covalent adduct, thus showing the utility of FP-probes towards ABPP applications.