Irreversible inhibition

Inhibitors that bind irreversibly to an enzyme frequently form a covalent bond to an amino acid residue at or near the active site and permanently inactivate the enzyme.  Susceptible amino acid residues involve Cys and Ser residues that have reactive –OH and –SH groups respectively. The compound DIPF (diisopropylphosphofluoridate),  a component  of  nerve  gases  behaves  with  a Ser residue   in  the   active   site   of  the   enzyme   acetylcholinesterase  permanently inhibiting  the enzyme  and preventing  the transmission  of nerve impulses shown in the figure. Iodoacetamide  modifies Cys residues and while may be used as  a  diagnostic  tool  in  determining   whether  one  or  more  Cys  residues  are needed  for  enzyme  activity that is shown in another figure.  The  antibiotic  penicillin  irreversibly inhibits  the  glycopeptide  transpeptidase  enzyme  which  forms  the  cross-links  in the bacterial cell wall through covalently attaching to a Ser residue in the active site of the enzyme.