Family A24


Summary Holotypes Alignment Tree Genomes Structure Literature


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Alignment Tree Genomes Literature

Summary for family A24

NamePeptidase family A24 (type IV prepilin peptidase family)
Family type peptidaseA24.001 - type 4 prepilin peptidase 1 (Pseudomonas aeruginosa), MEROPS Accession MER0000870 (peptidase unit: 50-281)
Content of familyPeptidase family A24 contains membrane-inserted endopeptidases.
History Identifier created: MEROPS 5.00 (20 April 2000)
The catalytic mechanism of the bacterial peptidase that processes type 4 prepilin (A24.001) has long been a puzzle, but it now seems that it is an aspartic peptidase. The archaean preflagellin peptidase (A24.016) is a distant homologue.
Catalytic typeAspartic
Active siteThe active site residues of the peptidases of family A24 are both aspartates (LaPointe & Taylor, 2000). In subfamily A24A, the two active-site Asp residues occur in the motifs Xaa-Xaa-Asp-Xaa-Xbb-Xcc-Xcc-Xcc-Xaa-Pro and Xaa-Gly-Xcc-Gly-Asp-Xaa-Lys-Xaa-Xaa-Xaa (where Xaa is hydrophobic, Xbb is charged and Xcc is any amino acid) (Rawlings & Barrett, 2004) (see the Alignment).
Activities and specificitiesThe prepilin peptidases (A24.001, A24.003) process type 4 pilin precursor proteins (prepilins) to their mature forms by removal of leader peptides. The leader peptides differ from those processed by signal peptidase I (S26.001) in that they are 5 - 8 residues long, rich in acidic amino acids, and immediately precede a 20-residue hydrophobic region. The consensus sequence of the cleavage site is GlyPhe. Following release of the signal peptide, the prepilin peptidase acts as a methyl transferase and methylates the newly-exposed N-terminal residue (Lory & Strom, 1997). Other protein precursors destined for secretion are also processed (Nunn & Lory, 1991).
Also in the family is preflagellin peptidase (A24.016). Some archaea possess a flagellum different from those found in bacteria that contain a flagellin protein that is synthesized as a precursor with a positively charged leader peptide; the leader peptide is removed by the preflagellin peptidase before the protein is incorporated into the filament (Bardy & Jarrel, 2002).
Molecular structureThe tertiary structure of the preflagellin peptidase from Methanococcus maripaludis has been solved, and shows a bundle of six transmembrane helices. The active site aspartates are on helices 1 and 4, and are far apart, implying that a conformational change is required to activate the peptidase (Hu et al., 2011). The structure is unique to family A24, and is the type structure for clan AD. The peptidases of subfamily A24A contain eight predicted transmembrane domains (five of which are included in the peptidase unit: see the Alignment).
Basis of clan assignmentType family of clan AD.
Distribution of family Bacteria details  
Archaea details  
Protozoa -  
Fungi -  
Plants details  
Animals -  
Viruses -  
Biological functionsType 4 prepilins are required for functions including type IV pilus formation, toxin and other enzyme secretion, gene transfer and biofilm formation (LaPointe & Taylor, 2000), and the pilins can perform these functions only after processing by a prepilin peptidase.
ReviewsDupuy et al. (2004)
Statistics for family A24Sequences:6160
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily A24A
Name Peptidase subfamily A24A
Subfamily type peptidase A24.001 - type 4 prepilin peptidase 1 (Pseudomonas aeruginosa), MEROPS Accession MER0000870 (peptidase unit: 50-281)
Active site residues D149 D213 
Statistics Sequences: 6013
Identifiers: 7
Identifiers with PDB entries: 0
Other databases INTERPRO IPR000045
PFAM PF01478
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
type 4 prepilin peptidase 1A24.001-
type 4 prepilin peptidase 2A24.003-
PibD peptidaseA24.017-
EppA peptidaseA24.018-
ComC peptidaseA24.019-
PppA protein (Escherichia coli)A24.A01-
gspO g.p. (Escherichia coli)A24.A10-
subfamily A24A non-peptidase homologuesnon-peptidase homologue-
subfamily A24A unassigned peptidasesunassigned-
Subfamily A24B
Name Peptidase subfamily A24B
Subfamily type peptidase A24.016 - FlaK peptidase (Methanococcus maripaludis), MEROPS Accession MER0019305 (peptidase unit: 1-144)
Active site residues D18 D79 
Statistics Sequences: 132
Identifiers: 1
Identifiers with PDB entries: 1
Other databases INTERPRO IPR000045
PFAM PF01478
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
FlaK peptidaseA24.016Yes
subfamily A24B non-peptidase homologuesnon-peptidase homologue-
subfamily A24B unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
family A24 non-peptidase homologuesnon-peptidase homologue-
family A24 unassigned peptidasesunassigned-