rgpB

RgpB is a cysteine protease produced by the periodontal pathogen Porphyromonas gingivalis. It belongs to the arginine‑specific gingipain family and is one of three related enzymes (RgpA, RgpB, Kgp) that cleave peptide bonds after arginine or lysine residues. RgpB is secreted as a soluble protein but can also associate with the bacterial outer membrane and cell surface, contributing to virulence by degrading host proteins, manipulating immune signaling and promoting tissue destruction.

The enzyme contains a catalytic cysteine residue that, together with histidine and asparagine, forms a catalytic triad. Its active site is located in a cleft that accommodates the P1 arginine side chain, ensuring substrate specificity. Structural studies, including X‑ray crystallography, have revealed a typical α/β‑fold with a propeptide region that is cleaved during maturation. Genetic studies show that the rgpB gene is regulated by quorum‑sensing mechanisms and during iron limitation, which aligns its expression with environmental cues encountered during infection.

RgpB activity is essential for maximal virulence in animal models of periodontal disease. Inhibition of RgpB using specific peptide or small‑molecule inhibitors reduces bone loss and bacterial colonization, making it a target of interest for therapeutic intervention. The enzyme also generates peptides that act as immunomodulators; for example, some RgpB hydrolysis products can bind to toll‑like receptor 4, influencing inflammatory signaling.

Because of its central role in host tissue destruction, immune evasion, and bacterial fitness, RgpB remains a major focus of research in periodontology and microbial pathogenesis.