Summary for clan SK

Summary Alignment Structure Literature
Clan type peptidaseS14.001 - peptidase Clp (type 1) (Escherichia coli), MEROPS Accession MER0000474 (peptidase unit: 1-207); PDB accession 1TYF_A
HistoryMEROPS 2.00 (14 January 1998)
DescriptionSerine nucleophile; catalytic residues in the order Ser, His, Asp in sequence
Contents of clanPeptidase clan SK contains families of serine peptidases.
EvidenceLocal similarities in amino acid sequence link families S14 and S49 (Bolhuis et al., 1999; Liu & Mushegian, 2004). Family S41 is linked in to the clan by the protein fold of S41.001, which is similar to that of clpP peptidase (S14.001).
Catalytic mechanismClan SK is exceptional in that it contains peptidases with a variety of arrangements of active site residues. In family S14, there is a catalytic triad in the order Ser, His, Asp. In family S41, the catalytic residues differ between the subfamilies: in subfamily A there is a Ser, Lys dyad whereas in subfamily B four residues are important in the order Ser, His, Ser, Glu with the second Ser being the nucleophile. Subfamily S41B differs from other families in the clan in that the general base (His) precedes the nucleophile, and this is explained by sequence rearrangement. Only the active site serine is known with certainty in family S49.
All three families contain a highly conserved Gly that helps to stabilise the oxyanion intermediate in catalysis. This commonly occurs in the motif Xaa-Pro-Gly-Gly, in which Xaa is Ser or Thr in families S14 and S49 (see the Alignments).
Peptidase activityAll the peptidases in the clan are endopeptidases.
Protein foldTertiary structures have been determined for members of families S14 (peptidase clp, S14.001, Wang et al., 1997) and S41 (C-terminal processing peptidase-2, S41.002, Liao et al., 2000; and the tricorn core peptidase, S41.005, Brandstetter et al., 2001). The structure of a single clpP monomer has been described as a 'superhelix' containing four helices, three of which are each associated with two beta-strands. One helix extends to give the molecule a shape like a hatchet, and its associated sheets carry the active site His and Asp. The catalytic serine is at the start of a helix and the active site is formed between the 'handle' and the 'blade' of the hatchet. In C-terminal processing peptidase-2 there are additional domains. In the tricorn core peptidase, there is a PDZ domain nested within the peptidase unit, and some structural rearrangement has occurred such that the order of the catalytic Ser and Lys are reversed in the chain with respect to the Ser and His of clpP.
Homologous non-peptidase familiesA similar fold is found in a number of other proteins including acetyl-coenzyme A carboxylase, subunit A of glutaconyl-CoA decarboxylase, 4-chlorobenzoyl-CoA dehalogenase, enoyl-CoA hydratase, naphthoate synthase MenB and methylmalonyl CoA decarboxylase (see SCOP sunid 52096). There is similarity in the location of the active site residues between some of these enzymes (Murzin, 1998).
Other databases PFAMCL0127


Family Family Type Peptidase Structure
S14 peptidase Clp (type 1) (Escherichia coli) Yes
S41 C-terminal processing peptidase-1 (Escherichia coli) Yes
S49 signal peptide peptidase A (Escherichia coli) Yes

Distribution of clan SK among Kingdoms of Organisms