Summary for clan CE

Summary Alignment Structure Literature
Clan type peptidaseC05.001 - adenain (human adenovirus type 2), MEROPS Accession MER0000802 (peptidase unit: 1-204); PDB accession 1AVP_A
HistoryPerspect.Drug Discov.Des. 6:1-11 (1996)
DescriptionCysteine nucleophile; catalytic residues in the order His, Glu (or Asp), Cys in sequence
Contents of clanClan CE contains cysteine endopeptidases.
EvidenceThe order of active site residues in clan CE is His, Asp (or Asn), Gln and Cys (see the Alignment). Families without determined tertiary structures are included in the clan because the catalytic residues are in the same order as in adenain (C05.001), the type example for the clan.
Catalytic mechanismCatalysis is thought to be similar to that of papain (C01.001) proceeding through an acyl enzyme intermediate. The catalytic dyad (His, Cys) is complemented by Glu71 (most commonly Asp, in the clan CE as a whole), which has the role of orientating the imidazolium ring of the catalytic His54, and Gln115, which helps form the oxynion hole.
Peptidase activitySeveral of the peptidases in clan CE show specificity for cleavage after diglycine. It has been suggested that the preference for Gly in P1 that is shown by many peptidases in clan CE (as well as some in clan CA) is due to the presence of tryptophan or another aromatic residue following the catalytic histidine in the sequence (Golubtsov et al., 2006). Adenain is synthesized in an inactive form that requires peptide cofactors, the 11-amino acid peptide pVIc (GVQSLKRRRCF) and the viral DNA for activity (McGrath et al., 2001).
Protein foldTertiary structures have been determined for members of families C5 (Ding et al., 1996) and C48 (Reverter et al., 2005). Peptidases in clan CE have two structural subdomains with the active site between them. One subdomain is a beta barrel carrying the active site His and Glu (or Asp) and the second subdomain consists of a helical bundle, one of which carries the catalytic Cys. The structure is similar to that of clan CA, except that the order of subdomains is reversed.
EvolutionIt is very possible that clan CE shares an origin with clan CA, the characteristic folds being related by circular permutation, as is suggested in the SCOP database [sunid 54001]. The sequences of each of the type peptidases of clans CA and CE contain two sequence motifs that are generally conserved throughout the clans. These motifs contain the key catalytic residues, Cys and His, and are Gln-(Xaa)n1-Cys and His-(Xaa)n2-Asn/Glu (where n1 = 5 or 6) and n2 = 15 or 16), respectively. In clan CA the Cys-motif occurs first in the sequence and in clan CE the His-motif occurs first. The idea that the two parts of the catalytic site have exchanged positions in a circular permutation during the evolution of the clans is consistent with the protein folds, as can be seen in the three-dimensional and two-dimensional representations of the structures in the MEROPS database.
Activation mechanismThe roles of two conserved cysteine residues involved in the activation of adenain were investigated (McGrath et al., 2001).
Other databases PFAMCL0134


Family Family Type Peptidase Structure
C5 adenain (human adenovirus type 2) Yes
C48 Ulp1 peptidase (Saccharomyces cerevisiae) Yes
C55 YopJ protein (Yersinia pseudotuberculosis) -
C57 vaccinia virus I7L processing peptidase (Vaccinia virus) -
C63 African swine fever virus processing peptidase (African swine fever virus) -
C79 ElaD peptidase ({Escherichia}-type) (Escherichia coli) -

Distribution of clan CE among Kingdoms of Organisms