General information on IdeS Protease
IdeS (Immunoglobulin G-degrading enzyme of Streptococcus pyogenes) is an immunoglobulin-degrading protease that cleaves the hinge region of IgG antibodies. The enzyme cleaves IgG from all human isotypes (IgG1, IgG2, IgG3, and IgG4). Additionally, it was shown to cleave IgG from other species (rabbit, sheep, rodents, etc.) and formats (i.e., Fc-fusion proteins, Antibody-drug conjugates – ADC).
This protease yields two distinct fragments with high specificity and reproducibility – one F(ab’)2 fragment at about 110 kDa and two identical ½ Fc fragments at about 20 kDa each. The hydrolysis was shown to occur on a defined site between two glycine residues in positions 236 and 237 in the lower hinge region of the heavy chain. This contrasts with papain, another well-known IgG-degrading protease, that cleaves in the upper hinge region yielding a 50 kDa Fc fragment and two identical Fab fragments at 50 kDa each.
The IdeS protease was first discovered in Streptococcus pyogenes, an important human pathogen. It is a cysteine endoprotease with a unique degree of specificity. Due to its stability and ease of use, IdeS can be employed for the characterization of antibodies, Fc-fusion proteins, or ADC. Recent studies have also shown its potential for the treatment of some autoimmune disorders including arthritis.
On its original host, IdeS ensures S. pyogenes’ survival by circumventing IgG-mediated immune responses and modulating the inflammatory response. The protease was found to be conserved among many strains of S. pyogenes hinting at its importance for pathogenicity. By cleaving IgG antibodies into two functional fragments, IdeS prevents the recruitment of immune cells and likely interferes with the recognition of the fragmented IgG by complement and Fc receptors. In vitro, the enzyme produces high-purity fragments and requires short incubation times (30 minutes), making it very useful for a wide range of applications.