C5a peptidase (ScpA) activity towards human type II and type III interferons.

C5a peptidase, also known as ScpA, is a surface associated serine protease derived from Streptococcus pyogenes and has been described as an important factor in streptococcus virulence, capable of cleaving complement components C5a, C3 and C3a. Although the interactions of ScpA with complement components is well studied, extensive screening of ScpA activity against other pro-inflammatory cytokines is lacking. Here, ScpA's ability to cleave human pro-inflammatory cytokines was tested, revealing its ability to cleave human IFNγ, IFNλ1, IFNλ2, C5, IL-37 but with significantly reduced activities.

The 1.7 Å crystal structure of the C5a peptidase from Streptococcus agalactiae (ScpB) reveals an active site competent for catalysis.

A 1.7 Å structure is presented for an active form of the virulence factor ScpB, the C5a peptidase from Streptococcus agalactiae. The previously reported structure of the ScpB active site mutant exhibited a large separation (~20 Å) between the catalytic His and Ser residues.

Impact of Propeptide Cleavage on the Stability and Activity of a Streptococcal Immunomodulatory C5a Peptidase for Biopharmaceutical Development.

Posttranslational modifications of proteins can impact their therapeutic efficacy, stability, and potential for pharmaceutical development. The Group AC5a peptidase (ScpA) is a multi-domain protein composed of an N-terminal signal peptide, a catalytic domain (including propeptide), three fibronectin domains, and cell membrane-associated domains. It is one of several proteins produced by Group Aknown to cleave components of the human complement system.

Exosite binding modulates the specificity of the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease.

The C5a peptidase from (ScpA) is a highly specific enzyme with potential therapeutic value. ScpA is a good model for studying determinants of specificity in the multidomain immunomodulatory enzymes (IMEs), which comprise a large family of bacterial surface proteases. The surface exposed region of ScpA has 5 main domains which includes 3 C-terminal Fn3-like domains (Fn1, Fn2 and Fn3) (Kagawa et al.

Enzyme kinetic and binding studies identify determinants of specificity for the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease.

The Streptococcal C5a peptidase (ScpA) specifically inactivates the human complement factor hC5a, a potent anaphylatoxin recently identified as a therapeutic target for treatment of COVID-19 infections. Biologics used to modulate hC5a are predominantly monoclonal antibodies. Here we present data to support an alternative therapeutic approach based on the specific inactivation of hC5a by ScpA in studies using recombinant hC5a (rhC5a).