Name | Peptidase family C25 (gingipain family) |
Family type peptidase | C25.001 - gingipain RgpA (Porphyromonas gingivalis), MEROPS Accession MER0001351 (peptidase unit: 228-578) |
Content of family | Peptidase family C25 contains cysteine endopeptidases from bacteria, notably gingipain R (C25.001) and gingipain K (C25.002). |
History |
Identifier created: Perspect.Drug Discov.Des. 6:1-11 (1996) The proteolytic activity of Porphyromonas gingivalis (formerly Bacteroides gingivalis) was characterised by Carlsson et al. (1984), and the peptidase was first termed gingivain (Shah et al., 1991 and then gingipain. Gingipain proved to comprise two peptidases, which are termed gingipain-R (C25.001) and gingipain-K (C25.002) in MEROPS (Potempa & Travis, 1995). Porphyromonas gingivalis is a black-pigmented bacterium that is one of the causal organisms of periodontitis (Imamura et al., 1994). The amino acid sequences of the gingipains show that they belong to a distinct family of cysteine peptidases, C25 in MEROPS. |
Catalytic type | Cysteine |
Active site residues | H438 C471 |
Active site | There is a His/Cys catalytic dyad, in a sequence motif characteristic of clan CD (Chen et al., 1998) (see the Alignment). |
Activities and specificities | Gingipains R and K are endopeptidases with specificity for arginyl and lysyl bonds, respectively. Like other cysteine peptidases, they require reducing conditions for activity. They are maximally active at approximately neutral pH. |
Inhibitors | General inhibitors of cysteine peptidases such as iodoacetamide, iodoacetic acid and N-ethylmaleimide, inactivate the enzymes slowly at rather high concentrations (10 mM). E-64 inhibits gingipain R only in a competitive, reversible manner, probably acting as an arginine analogue. Gingipain R, but not gingipain K, is also sensitive to inhibition by leupeptin and antipain. Peptidyl chloromethanes with a P1 Arg residue are extremely efficient irreversible inhibitors of gingipain R, and can be used for active site titration (Potempa et al., 1997). A nanomolar inhibitor of gingipain K has been described (Curtis et al., 2002). |
Molecular structure | The crystal structure of gingipain R shows a 435-residue, single-polypeptide chain organized into a catalytic domain and an immunoglobulin-like, hemagglutinin domain. The catalytic domain is divided into two subdomains comprising four- and six-stranded beta-sheets sandwiched between alpha-helices. Each subdomain has topological similarities to the p20-p10 heterodimer of caspase-1 (C14.001). The second subdomain contains the Cys/His catalytic dyad and a nearby Glu. The S1 specificity pocket contains an Asp residue that is believed to be responsible for the specificity preference for Arg in P1 (Eichinger et al., 1999). |
Clan | CD |
Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of caspase 1, the type example for clan CD. |