Family C40


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family C40

Family type peptidaseC40.001 - dipeptidyl-peptidase VI (bacteria) (Lysinibacillus sphaericus), MEROPS Accession MER0001322 (peptidase unit: 154-271)
Content of familyPeptidase family C40 contains bacterial cell-wall modifying enzymes.
History Identifier created: Proteolysis in Cell Function, pp13-21, IOS Press, Amsterdam (1997)
Catalytic typeCysteine
Active site residuesC178 H224 H,N,Q,E236 
Active siteThe peptidase units of dipeptidylpeptidase VI (DPP VI; C40.001) and the other proteins assigned to family C40 are the C-terminal 110-residue segments of the proteins. These contain single conserved cysteine and histidine residues that form a catalytic triad in the order Cys, His, His (see the Alignment). These were confirmed from the solution structure of the spr gene product from Escherichia coli (Aramini et al., 2008). A catalytic triad with two histidines is also found in serine peptidases from clan SH.
On the basis of Psi-BLAST searches starting from peptidases of family C40, Anantharaman & Aravind, 2003 described the 'NlpC/P60 superfamily' of proteins.
Activities and specificitiesDPP VI hydrolyses substrates of the general structure L-Ala-gamma-D-GluL-Zaa-Yaa, in which Zaa is a di-amino acid such as L-lysine or diaminopimelic acid, and Yaa is D-Ala or D-Ala-D-Ala. Activity is stimulated by 5 mM EDTA and 1 mM DTT.
InhibitorsDPP VI is inhibited by N-ethylmaleimide, iodoacetamide and phydroxymercuribenzoate.
Molecular structureThe tertiary structures of the gene products spr from Escherichia coli (Aramini et al., 2008), Ava_3396 from Anabaena variabilis and Npun0240 from Nostoc punctiforme (both unpublished) have been solved. All show structures reminiscent of the papain fold, with two subdomains, one consisting of a helical bundle and which bears the catalytic Cys, the other a beta barrel bearing the other active site residues. Unlike papain, where the catalytic Cys is at the N-terminus of a helix, in the structures from family C40 the active site Cys is at the C-terminus of a helix, which means the sequence must run in the opposite direction to that in papain. No similarity between the structures can be detected using the DALI algorithm (Holm & Sander, 1995). The structural resemblances are therefore assumed to be derived from convergent rather than divergent evolution, and proteins in C40 are assigned to the clan CO. All members of this family have either a signal peptide or a transmembrane region, indicating a cell-surface location.
Basis of clan assignmentType family of clan CO.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsDPP VI is a cytoplasmic enzyme best characterised from Bacillus sphaericus that is expressed during sporulation, and is responsible for the degradation of bacterial cell wall components (Guinand, 2004). LytF (C40.002) and LytE (C40.003) of B. subtilis hydrolyse the bacterial cell wall peptidoglycan, and are cell-separating enzymes (Yamamoto et al., 2003).
Statistics for family C40Sequences:13452
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR000064
PFAM PF00877
PFAM PF05382
SCOP 142873
Peptidases and Homologues MEROPS ID Structure
dipeptidyl-peptidase VI (bacteria)C40.001-
murein peptidase LytFC40.002-
murein peptidase lytEC40.003-
spr peptidaseC40.004Yes
PgdS peptidaseC40.005-
PgpA peptidaseC40.006-
YddH peptidaseC40.007-
CwlS peptidase (Bacillus sp.)C40.008-
NLP/P60 (Nostoc punctiforme)-like putative peptidaseC40.009Yes
CwlO peptidase (Bacillus sp.)C40.010-
RipA peptidoglycan hydrolaseC40.011-
RipB peptidoglycan hydrolaseC40.012-
YdhO protein (Escherichia coli)C40.013-
BacL1 peptidase ([Enterococcus faecalis)C40.014-
NlpC protein (Escherichia coli)C40.A01-
I33_2179 protein (Bacillus subtilis)C40.A06-
I33_1064 protein (Bacillus subtilis)C40.A07-
I33_1070 protein (Bacillus subtilis)C40.A08-
BSSC8_33880 (Bacillus subtilis)C40.A09-
phosphatase-associated protein (Bacillus subtilis)C40.A10-
family C40 non-peptidase homologuesnon-peptidase homologue-
family C40 unassigned peptidasesunassignedYes