Glutamyl endopeptidase GluV8

Glutamyl endopeptidase is in S. aureus expressed from the gene sspA within the operon ssp. Downstream of sspA, the operon also includes the genes of the cysteine protease staphopain B (sspB) and of staphostatin B (sspC; specific inhibitor of staphopain B). Glutamyl endopeptidase is largely co-expressed with the other major proteases of S. aureus: aureolysin, staphopain A, and staphopain B. The transcription of ssp, that occurs via a promoter controlled by "housekeeping" sigma factor σA, is up-regulated by accessory gene regulator agr, while it is repressed by staphylococcal accessory regulator sarA and by alternative sigma factor σB (a stress response modulator of Gram-positive bacteria). ssp expression is highly expressed in post-exponential growth phase. The sspA gene has a high prevalence in the genome of both commensal- and pathogenic-type S. aureus strains. == Activation ==

Glutamyl endopeptidase is expressed as a zymogen that, in order to become fully active, has been modified both through autocatalysis and through cleavage by the metalloprotease aureolysin. == Function ==

Glutamyl endopeptidase proteolytically activates the zymogen of the cysteine protease staphopain B (staphopain A is activated through and independent process). The bacterial protease has a narrow specificity, with a strict preference for catalyzing hydrolysis of proteins after negatively charged amino acids, especially glutamic acid, and to some extent aspartic acid. Aspartic acid is cleaved mainly when followed by a small amino acid, such as glycine. Glutamyl endopeptidase can furthermore cleave a wide array bacterial surface proteins, including fibronectin-binding proteins and protein A, potentially acting as a self-regulatory mechanism. == Biological significance ==

An immunization survey of human serum samples suggests that exposure to glutamyl endopeptidase is common, although a correlation to any specific type of infection could not be established. Glutamyl endopeptidase is indicated to participate in control and dissemination in bacterial biofilms. The protease can contribute to infection symptoms, e.g. pain and edema through increased vascular permeability by activating kinin. == References ==