PMSF is an inhibitor of:
Phenylmethylsulfonyl fluoride known as PMSF is prototypical irreversible inhibitor of serine protease class widely used in protein biochemistry to preserve extracts. Electrophilic sulfonyl fluoride reacts via nucleophilic attack of activated serine hydroxyl oxygen in catalytic triad Asp102 His57 Ser195 chymotrypsin numbering where histidine acts as general base accepting proton increasing nucleophilicity of serine oxygen. Sulfonyl group transferred forming covalent O-sulfonyl derivative phenylmethylsulfonyl enzyme, fluoride anion expelled, blocking deacylation step of catalytic cycle where water would attack acyl-enzyme intermediate. Enzyme rendered permanently inactive because sulfonyl ester hydrolysis extremely slow half-life days. Targets include trypsin, chymotrypsin, thrombin coagulation protease cleaving fibrinogen, plasmin fibrinolysis, elastase, kallikrein kinin system, and some esterases. PMSF also sulfonylates catalytic cysteine in certain cysteine proteases at higher pH above eight due to thiolate nucleophilicity but primary spectrum serine. This mechanistic insight supports diagnostic and therapeutic applications while reinforcing core immunological and cell biology principles taught in advanced curricula.
Ref: Gold & Fahrney Biochemistry 1964 PMSF sulfonylation Ser195 catalytic triad; Sambrook Molecular Cloning serine protease irreversible inhibitor.