1. Figure 4 C-Terminal protein citrullination catalysed
by Porphyromonas gingivalis peptidylarginine deiminase (PPAD)
Figure 4 | C-Terminal protein citrullination catalysed by Porphyromonas gingivalis peptidylarginine deiminase (PPAD). a | The molecular architecture of PPAD generally resembles that of human peptidylarginine deiminases (PADs) 2 and 4, with the molecule consisting of an α/β propeller catalytic domain followed by an Ig-like domain (IgSF). However, in PPAD, a steric hindrance of protruding loops surrounding the active site cleft (shown as a thick blue line) limit interactions between the substrate and the main chain of the reactive site cleft to only one side of a deiminated arginine side chain, while the arginine guanidine group interacts with the catalytic residues of PPAD (Asp130, Asp238 and His226)120. In addition, the carboxylate of the C-terminal arginine and the carbonyl of the preceding peptide bond are firmly anchored by salt bridges and hydrogen bonds to residues (Arg152, Arg154 and Tyr233) lining the substrate-binding cleft of PPAD120. b | These differences in substrate binding between PPAD and human PADs mechanistically explain why PPAD has a strong preference for C-terminal arginine residues. PPAD catalyses a reaction in which a guanidine group is hydrolysed, releasing ammonia and forming a C-terminal citrulline residue.
Potempa, J. et al. (2017) The case for periodontitis in the pathogenesis of rheumatoid arthritis
Nat. Rev. Rheumatol. doi: /nrrheum