Porphyromonas gingivalis peptidylarginine deiminase (PPAD)

Porphyromonas gingivalis peptidylarginine deiminase (PPAD) is a unique bacterial enzyme secreted by the keystone periodontal pathogen Porphyromonas gingivalis [1, 2]. Unlike human peptidylarginine deiminases (PADs) which citrullinate internal arginine residues, PPAD specifically targets C-terminal arginine residues, typically those exposed by the proteolytic action of bacterial gingipains [3, 4]. This enzymatic process converts arginine into citrulline, leading to the modification of both bacterial and host proteins and the subsequent generation of neoantigens [4, 5]. These citrullinated neoantigens are recognized by the immune system, triggering the production of anti-citrullinated protein antibodies (ACPAs), which are highly specific biomarkers and drivers of rheumatoid arthritis (RA) [3, 5]. Because of its central role in the link between periodontitis and RA, PPAD is a primary therapeutic target for small-molecule inhibitors [4]. Developing selective PPAD inhibitors is a priority to avoid cross-reactivity with human PAD isoforms, which are essential for normal physiological processes like gene regulation and skin keratinization [1, 4].

Other names

Peptidyl-arginine deiminaseP. gingivalis PADProtein-arginine deiminasePAD_PORGI

Inhibition of the enzymatic conversion of C-terminal arginine residues to citrulline, thereby preventing the formation of citrullinated neoantigens and the subsequent autoimmune response.