Rapid IgG heavy chain cleavage by the streptococcal IgG endopeptidase IdeS is mediated by IdeS monomers and is not due to enzyme dimerization

• IdeS is a streptococcal protease specific for IgG.
• Cleavage of the first heavy chain is 100 fold faster than cleavage of the second chain.
• IdeS is fully active as a monomer.
• IdeS monomers rapidly inactivate effector functions of IgG.
• Accurate determination of IdeS properties allows future studies on the importance of the enzyme.

Streptococcus pyogenes employs an IgG specific endopeptidase, IdeS, to counteract the effector functions of specific IgG. The physiological significant step in disarming specific IgG is the cleavage of one IgG heavy chain. So far, characterizations of IdeS enzymatic activity have employed techniques that failed to differentiate between the first and the second cleavage step. The present data demonstrate that IdeS is active as a monomer and that IdeS activity follows classical Michaelis–Menten kinetics arguing against the previously proposed formation of a functional IdeS dimer. Our results show that IdeS inactivates IgG 100-fold faster than previously reported.