IdeS from Streptococcus pyogenes, also known as Mac-1, is an endopeptidase with specificity for IgG. The bacterial protein Mac-1 adopts an alpha/beta fold, with 14 beta strands and 9 alpha helices. The N-terminal domain is made up predominantly of alpha helices, whereas the C-terminal domain consists predominantly of beta sheets. Mac 1 blocks polymorphonuclear opsonophagocytosis, inhibits the production of reactive oxygen species and contains IgG endopeptidase activity.IdeS is a unique enzyme that digests IgG at a specific site below the hinge region, generating a homogenous pool of F(ab‘)2 and Fc/2 fragments. IdeS digests all subclasses of human, and some classes of monkey, rabbit and sheep IgG. It has limited activity on mouse IgG2a and IgG3 - for digestion of these antibody species. IdeS is cloned from Streptococcus pyogenes and expressed in E. coli.