Arginine-specific gingipain (Gingipain R) (Rgp)

Arginine-specific gingipain (Gingipain R) is a major virulence factor produced by the periodontal pathogen Porphyromonas gingivalis (UniProt P45954, P56630). It functions as a cysteine protease that specifically cleaves peptide bonds at the C-terminal of arginine residues, facilitating bacterial nutrient acquisition and host immune system subversion (PubMed: 10591171). In the context of periodontitis, Gingipain R degrades collagen and other extracellular matrix components, leading to tissue destruction. Beyond the oral cavity, Gingipain R has been identified in the brains of Alzheimer's disease patients, where it is hypothesized to contribute to neurodegeneration through tau protein cleavage and the induction of neuroinflammation (Science Advances, 2019, 5(1):eaau3333). Therapeutic efforts have focused on small-molecule inhibitors like Atuzaginstat (COR388) to block these proteolytic activities, although clinical development has faced hurdles such as liver toxicity (ClinicalTrials.gov: NCT03820388).

Other names

RgpARgpBArginine-specific cysteine proteaseGingipain R1Gingipain R2Arg-gingipain

Small molecule inhibition of the arginine-specific cysteine protease activity to prevent host protein degradation and bacterial virulence.