Family S33


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family S33

Family type peptidaseS33.001 - prolyl aminopeptidase (Neisseria gonorrhoeae), MEROPS Accession MER0000431 (peptidase unit: 1-310)
Content of familyPeptidase family S33 contains mainly exopeptidases that act at the N-terminus of peptides.
History Identifier created: Methods Enzymol. 244:19-61 (1994)
Catalytic typeSerine
Active site residuesS107 D260 H287 
Active siteThe active site residues are in the order Ser, Asp, His in the sequence. The active site Ser occurs within the motif Gly-Xaa-Ser-Xbb-Gly, in which Xaa can be any residue and Xbb is most often hydrophobic (see the Alignment).
Activities and specificitiesProlyl aminopeptidase (S33.001) releases an N-terminal residue from a peptide, preferably (but not exclusively) a proline. A typical synthetic substrate is ProNHMec. Prolyl aminopeptidase from Xanthomonas campestris can also act as a D-AlaL-Leu dipeptidase (Alonso & Garcia, 1996). The archaean prolyl aminopeptidase is also interacting factor F1 (S33.005) of the tricorn peptidase complex (XP01-001). Tripeptidyl-peptidases A (S33.002), B (S33.006)and C (S33.007) from Streptomyces species release a tripeptide from the N-terminus of a peptide. Unusually, a homologue from Streptomyces coelicolor has been shown to be an endopeptidase with chymotrypsin-like specificity (Nagy et al., 2003). There are a large number of non-peptidase homologues in family S33, including enzymes such as epoxide hydrolases.
InhibitorsOnly some members of the family are inhibited by the general serine peptidase inhibitors DFP and PMSF. Prolyl aminopeptidase from Xanthomonas campestris is sensitive to thiol-blocking compounds such as ethyl mercury thiosalicylate and was initially misidentified as a cysteine peptidase (Kitazono et al., 2004).
Molecular structureThe tertiary structure of prolyl aminopeptidase has been determined (Medrano et al., 1998) and shows a two-domain molecule with the active site between the domains. The larger domain adopts the alpha/beta hydrolase fold and the structure similar to that of serine carboxypeptidase Y (S10.001). Hence family S33 is included in clan SC. A cysteine residue close to the active site may explain the thiol dependence of prolyl aminopeptidase. The prolyl aminopeptidase from Xanthomonas crystallized as a homodimer, but that from Serratia marcescans crystallized as a monomer.
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of serine carboxypeptidase D, the type example of clan SC.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsMost members of the family are synthesized with signal peptides and are thus either secreted or periplasmic enzymes. Prolyl aminopeptidase activity is not essential for bacterial growth, but may confer a selective advantage allowing a bacterium to utilize proline-rich substrates.
Pharmaceutical and biotech relevanceProlinase (S33.004) from Lactobacillus is used in cheese making. Presence of prolyl aminopeptidase has been used as a diagnostic tool for several pathogens including Clostridrium difficile and Candida albicans. Prolyl aminopeptidase is also used as a reagent in assays of other enzymes such as methionyl aminopeptidase (M24.001), performing a second cleavage to release the detectable C-terminal blocking group of the substrate.
Statistics for family S33Sequences:28544
Identifiers with PDB entries:22
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH
PFAM PF00561
PFAM PF00975
PFAM PF03096
PFAM PF07819
PFAM PF08386
PFAM PF11339
PFAM PF12146
PFAM PF12147
PFAM PF12695
PFAM PF12697
SCOP 53509
Peptidases and Homologues MEROPS ID Structure
prolyl aminopeptidaseS33.001Yes
tripeptidyl-peptidase AS33.002-
leucine aminopeptidase pepL (Lactobacillus delbrueckii)S33.003-
prolyl dipeptidase (Lactobacillus-type)S33.004-
tricorn interacting factor F1S33.005Yes
tripeptidyl-peptidase BS33.006-
tripeptidyl-peptidase CS33.007-
prolyl aminopeptidase 2S33.008-
Mername-AA086 putative peptidaseS33.009-
SCO7095-type peptidaseS33.010-
epoxide hydrolase-like putative peptidaseS33.011-
Loc328574-like proteinS33.012-
abhydrolase domain-containing protein 4S33.013-
2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (Burkholderia-type)S33.016Yes
PLN02872 protein (Homo sapiens-type)S33.017-
LIPF protein (Homo sapiens)S33.018-
COG0429 protein (Homo sapiens)S33.019-
LIPJ protein (Homo sapiens)S33.020-
iminopeptidase I (Lactobacillus delbrueckii) and similarS33.021-
Lpx1 peptidase (Saccharomyces cerevisiae)S33.022Yes
Hip1 peptidase (Mycobacterium tuberculosis)S33.023Yes
epoxide hydrolaseS33.971Yes
mesoderm specific transcript proteinS33.972-
cytosolic epoxide hydrolaseS33.973Yes
similar to hypothetical protein FLJ22408S33.974-
CGI-58 putative peptidaseS33.975Yes
Williams-Beuren syndrome critical region protein 21 epoxide hydrolaseS33.976-
epoxide hydrolaseS33.977-
hypothetical protein flj22408 (epoxide hydrolase)S33.978-
monoglyceride lipaseS33.979Yes
monoglyceride lipaseS33.980-
hypothetical proteinS33.981-
valacyclovir hydrolaseS33.982Yes
Ccg1-interacting factor bS33.983Yes
protein phosphatase methylesterase 1S33.984Yes
NDRG4 proteinS33.986-
NDRG3 proteinS33.987-
Mername-AA229 peptidase homologueS33.988-
protein NDRG2-type non-peptidase homologueS33.989-
haloalkane dehalogenaseS33.990Yes
CPO-A2 (Streptomyces aureofaciens)-type chloroperoxidaseS33.991Yes
chloroperoxidase 1 (Streptomyces lividans-type)S33.992Yes
YJU3 (Saccharomyces cerevisiae)S33.993-
BioH protein (Escherichi coli)S33.994Yes
MhpC protein (Escherichi coli)S33.995Yes
YfbB protein (Escherichi coli)S33.996Yes
At4g36530 (Arabidopsis thaliana)S33.A01-
At5g38520 (Arabidopsis thaliana)S33.A02-
At5g19850 (Arabidopsis thaliana)-type peptidaseS33.A03-
At4g33180/At4g33190 (Arabidopsis thaliana)S33.A04-
At5g16120 (Arabidopsis thaliana)S33.A05-
At2g39410 (Arabidopsis thaliana)S33.A06-
At2g39400 (Arabidopsis thaliana)S33.A07-
At1g11090 (Arabidopsis thaliana)S33.A08-
At4g36610 (Arabidopsis thaliana)S33.A09-
At1g17430 (Arabidopsis thaliana)S33.A10-
At5g11650 (Arabidopsis thaliana)S33.A11-
At1g73480 (Arabidopsis thaliana)S33.A12-
At2g47630 (Arabidopsis thaliana)S33.A13-
At5g21950 (Arabidopsis thaliana)S33.A14-
At2g18360 (Arabidopsis thaliana)S33.A15-
At5g39220 (Arabidopsis thaliana)S33.A16-
At1g18360 (Arabidopsis thaliana)S33.A17-
At3g03990 (Arabidopsis thaliana)-type peptidaseS33.A18Yes
At1g78210 (Arabidopsis thaliana)S33.A19-
At2g39420 (Arabidopsis thaliana)S33.A20-
At4g10030 (Arabidopsis thaliana)S33.A21-
At1g74280 (Arabidopsis thaliana)S33.A22-
At3g52570 (Arabidopsis thaliana)S33.A23-
At5g19290 (Arabidopsis thaliana)S33.A24-
At5g14980 (Arabidopsis thaliana)S33.A25-
At4g24150 (Arabidopsis thaliana)S33.A26-
At1g64670 (Arabidopsis thaliana)S33.A27-
At5g41900 (Arabidopsis thaliana)S33.A28-
At4g37470 (Arabidopsis thaliana)-type peptidaseS33.A29Yes
At3g09690 (Arabidopsis thaliana)S33.A30-
At3g55180 (Arabidopsis thaliana)S33.A31-
At5g02970 (Arabidopsis thaliana)S33.A32-
At5g09430 (Arabidopsis thaliana)S33.A33-
At5g13800 (Arabidopsis thaliana)S33.A34-
At1g72620 (Arabidopsis thaliana)S33.A35-
At1g68900 (Arabidopsis thaliana)S33.A36-
At1g52760 (Arabidopsis thaliana)-type peptidaseS33.A37-
At4g10050 (Arabidopsis thaliana)S33.A38-
At1g77420 (Arabidopsis thaliana)S33.A39-
homoserine acetyltransferase (Saccharomyces cerevisiae)S33.A41-
hypothetical protein ECM18 (Saccharomyces cerevisiae)S33.A42-
chromosome XII reading frame ORF ylr099c (Saccharomyces cerevisiae)S33.A43-
YheT protein (Escherichi coli)S33.A46-
YnbC protein (Escherichi coli)S33.A54-
Abhd2a proteinS33.A56-
PLN02872 protein (Mus musculus)S33.A57-
lipase MS33.A58-
LOC628236 protein (Mus musculus)S33.A59-
LOC638393 protein (Mus musculus)S33.A60-
At2g15230 protein (Arabidopsis thaliana)S33.A61-
At1g73920 protein (Arabidopsis thaliana)S33.A62-
putative acetone-cyanohydrin lyase (Arabidopsis thaliana)S33.A63-
PLN02872 (Arabidopsis thaliana)S33.A64-
At1g15070 protein (Arabidopsis thaliana)S33.A65-
At5g53050 or MhpC protein (Arabidopsis thaliana)S33.A66-
T5L19.30 protein (Arabidopsis thaliana)S33.A67-
At1g18460 protein (Arabidopsis thaliana)S33.A68-
MES14 protein (Arabidopsis thaliana)S33.A69-
MES7 protein (Arabidopsis thaliana)S33.A70-
putative epoxide hydrolase (Arabidopsis thaliana)S33.A71-
At3g03230 protein (Arabidopsis thaliana)S33.A72-
AT5G17780 protein (Arabidopsis thaliana)S33.A73-
AT3G03240 protein (Arabidopsis thaliana)S33.A74-
F16a14.4 protein (Arabidopsis thaliana)S33.A75-
AT5G17720 protein (Arabidopsis thaliana)S33.A76-
F24B22.200 protein (Arabidopsis thaliana)S33.A77-
AT5G22460 protein (Arabidopsis thaliana)S33.A78-
At3g10840 protein (Arabidopsis thaliana)S33.A79-
MES10 protein (Arabidopsis thaliana)S33.A80-
kraken protein (Drosophila melanogaster)S33.A81-
CG18302 protein (Drosophila melanogaster)S33.A82-
CG18530 protein (Drosophila melanogaster)S33.A83-
CG1882 protein (Drosophila melanogaster)S33.A84-
CG2772 protein (Drosophila melanogaster)S33.A85-
CG6753 protein (Drosophila melanogaster)S33.A86-
IP09622 protein (Drosophila melanogaster)S33.A87-
lipase 1 (Drosophila melanogaster)S33.A88-
lipase 4 (Drosophila melanogaster)S33.A89-
male accessory gland protein (Drosophila melanogaster)S33.A90-
male accessory gland protein (Drosophila melanogaster)S33.A91-
CG5377 (Drosophila melanogaster)S33.A92-
CG7632 (Drosophila melanogaster)S33.A93-
CG11309 protein (Drosophila melanogaster)S33.A94-
CG5707 protein (Drosophila melanogaster)S33.A95-
CG15820 protein (Drosophila melanogaster)S33.A96-
CG5704 protein (Drosophila melanogaster)S33.A97-
CG15879 protein (Drosophila melanogaster)S33.A98-
K08D9.4 g.p. (Caenorhabditis elegans)S33.B01-
lipl-8 g.p. (Caenorhabditis elegans)S33.B02-
C31H5.1 g.p. (Caenorhabditis elegans)S33.B03-
F35H12.5 g.p. (Caenorhabditis elegans)S33.B04-
lipl-7 g.p. (Caenorhabditis elegans)S33.B05-
F10D2.10 g.p. (Caenorhabditis elegans)S33.B06-
lipl-4 g.p. (Caenorhabditis elegans)S33.B07-
Y73C8B.2 g.p. (Caenorhabditis elegans)S33.B08-
lipl-1 g.p. (Caenorhabditis elegans)S33.B09-
lipl-3 g.p. (Caenorhabditis elegans)S33.B10-
K01A2.5 g.p. (Caenorhabditis elegans)S33.B11-
B0464.9 g.p. (Caenorhabditis elegans)S33.B12-
Y55F3AM.10 g.p. (Caenorhabditis elegans)S33.B13-
PF3D7_1410100 g.p. (Plasmodium falciparum)S33.B15-
PF08_0022 g.p. (Plasmodium falciparum)S33.B16-
PF10_0018 g.p. (Plasmodium falciparum)S33.B17-
serhl (Brachydanio rerio)S33.B18-
family S33 non-peptidase homologuesnon-peptidase homologueYes
family S33 unassigned peptidasesunassignedYes