Arginine-specific gingipain B (RgpB)

Arginine-specific gingipain B (RgpB) is a major cysteine protease secreted by the anaerobic bacterium Porphyromonas gingivalis, a primary pathogen in chronic periodontitis (UniProt P95493). It functions as a critical virulence factor by degrading host proteins, including collagen and cytokines, and by facilitating immune evasion through the cleavage of complement factors (Potempa et al., 2000). RgpB specifically cleaves peptide bonds at the carbonyl side of arginine residues, a process essential for bacterial nutrient acquisition and tissue invasion. Research has demonstrated that RgpB is present in the brains of Alzheimer's disease patients, where it correlates with tau and ubiquitin pathology, suggesting a role in neurodegeneration (Dominy et al., Science Advances, 2019). This has led to the identification of RgpB as a therapeutic target, with small-molecule inhibitors like COR271 being developed to mitigate its proteolytic damage. While clinical development of gingipain inhibitors has faced challenges such as liver toxicity in related compounds like Atuzaginstat, RgpB remains a significant target for treating P. gingivalis-associated inflammatory and neurodegenerative conditions. The enzyme's ability to modulate the host immune response and promote chronic inflammation makes it a focal point for research into the systemic links between oral health and systemic diseases.

Other names

Gingipain R2Arg-gingipain BArginine-specific cysteine proteinase BRgp2

Small molecule inhibition of the cysteine protease active site, preventing the cleavage of host proteins and reducing bacterial virulence.