F
IPR002470

Peptidase S9A, prolyl oligopeptidase

InterPro entry
Short namePeptidase_S9A
Overlapping
homologous
superfamilies
 

Description

This group of serine peptidases belong to MEROPS peptidase family S9 (clan SC), subfamily S9A (prolyl oligopeptidase) which includes PREP and PREPL from human
[5]
, fungal prolyl oligopeptidases such as ophP, ledP, dbiP which are part of the gene cluster that mediates the biosynthesis of omphalotin A, lentinulin A, and dendrothelin A, respectively, methylated cyclic dodecapeptides with nematodicidal activity
[3, 4]
.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes
[1]
. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence
[1]
. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases
[1]
.

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base
[1]
. The geometric orientations of the catalytic residues are similar between families, despite different protein folds
[1]
. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC)
[1, 2]
.

References

1.Families of serine peptidases. Rawlings ND, Barrett AJ. Meth. Enzymol. 244, 19-61, (1994). View articlePMID: 7845208

2.Evolutionary families of peptidases. Rawlings ND, Barrett AJ. Biochem. J. 290 ( Pt 1), 205-18, (1993). View articlePMID: 8439290

3.A Self-Sacrificing N-Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin. Ramm S, Krawczyk B, Muhlenweg A, Poch A, Mosker E, Sussmuth RD. Angew Chem Int Ed Engl 56, 9994-9997, (2017). PMID: 28715095

4.Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A. Matabaro E, Kaspar H, Dahlin P, Bader DLV, Murar CE, Staubli F, Field CM, Bode JW, Kunzler M. Sci Rep 11, 3541, (2021). View articlePMID: 33574430

5.PREPL deficiency: delineation of the phenotype and development of a functional blood assay. Regal L, Martensson E, Maystadt I, Voermans N, Lederer D, Burlina A, Juan Fita MJ, Hoogeboom AJM, Olsson Engman M, Hollemans T, Schouten M, Meulemans S, Jonson T, Francois I, Gil Ortega D, Kamsteeg EJ, Creemers JWM. Genet Med 20, 109-118, (2018). View articlePMID: 28726805

GO terms

biological process

cellular component

  • None

Cross References

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