Summary for clan CD
Clan type peptidase | C14.001 - caspase-1 (Homo sapiens), MEROPS Accession MER0000850 (peptidase unit: 120-404); PDB accession 1ICE |
History | Perspect.Drug Discov.Des. 6:1-11 (1996) |
Description | Cysteine nucleophile; catalytic residues in the order His, Cys in sequence |
Contents of clan | Clan CD contains eight families of endopeptidases. |
Evidence | Clan CD contains families with a protein fold or sequence motifs similar to those found in the caspase family (C14). All families contain a His, Cys catalytic dyad. The catalytic His occurs in a His-Gly motif and is preceded by a block of hydrophobic residues; the catalytic Cys occurs in the motif Ala-Cys and is preceded by a second block of hydrophobic residues (Chen et al., 1998). |
Catalytic mechanism | The His, Cys catalytic dyad acts with a mechanism distinct from the Cys, His dyads in clan CA (Polgar, 2004). |
Peptidase activity | Specificity is strongly directed to the P1 residue of the substrate, which is normally Asn in family C13, Asp in family C14, and Arg (or sometimes Lys) in C11, C25 and C50. Glycosylphosphatidylinositol:protein transamidase (C13.005) is not a conventional endopeptidase, requiring removal of a C-terminal peptide before it can attach glycosylphosphatidylinositol anchors to newly synthesised proteins in the endoplasmic reticulum. |
Protein fold | Tertiary structures have been determined for members of families C14 (Walker et al., 1994) and C25 (Eichinger et al., 1999). These show alpha/beta proteins with a fold that consists of an alpha/beta/alpha sandwich. The beta sheet contains six strands (in the order 213456) and strand 6 is antiparallel to the rest. Other families are included in the clan because of the conservation of motifs around the catalytic residues (Chen et al., 1998). |
Homologous non-peptidase families | The fold is unique to members of clan CD. |
Activation mechanism | Clan CD members are activated in a number of different ways. Peptidases in family C11 are synthesised as proenzymes and require removal of an N-terminal propeptide for activation (Labrou & Rigden, 2004). Peptidases in families C14 are activated by dimerization without proteolysis or by internal limited proteolysis (Boatright & Salvesen, 2003). Prolegumain (C13.004) activates itself by cleavage of an asparaginyl bond in the acidic conditions of the lysosome (Chen et al., 2000). Ginginpains R (C25.001) and K (C25.002) are secreted and work together to autolytically remove their C-terminal haemaglutinin domain. |
Other databases
| PFAM | CL0093 |
| SCOP | 52129 |
Families
C11 |
clostripain (Hathewaya histolytica) |
- |
C123 |
RARP2 ({Rickettsia rickettsii}) (Rickettsia rickettsii) |
- |
C13 |
legumain (plant beta form) (Canavalia ensiformis) |
Yes |
C14 |
caspase-1 (Rattus norvegicus) |
Yes |
C25 |
gingipain RgpA (Porphyromonas gingivalis) |
Yes |
C50 |
separase (yeast-type) (Saccharomyces cerevisiae) |
- |
C80 |
RTX self-cleaving toxin (Vibrio cholerae) |
Yes |
C84 |
prtH peptidase ({Tannerella forsythensis} ATCC 43037) (Tannerella forsythia) |
- |
Distribution of clan CD among Kingdoms of Organisms