PROSITE documentation PDOC51276
PfpI endopeptidase domain profile


Pyrococcus furiosus protease I (PfpI) (EC 3.2.-.-) is an intracellular cysteine peptidase, characterized by its stability and proposed to represent the predominant proteolytic activity of this thermophilic archaebacterium. Pfpi-like proteins have been found in bacteria, archaea, in some plants and in amoebas.

The structure of P. horikoshii PfpI shows an α/β sandwich fold, which consists of a central β sheet flanked by two helices and two strands on one side, and by six helices and two strands on the other side (see <PDB:1G2I>). The fold resembles that of glutamine amidotransferases (GATase) of class I, which are characterized by a conserved Cys-His-Glu active site (see <PDOC00405>). The catalytically essential cysteine is located at a nucleophile elbow. PfpI forms a hexameric structure and the active sites are formed at the interfaces between three pairs of monomers. Cys and His form a triad with a glutamate residue from an adjacent monomer [1]. Pfpi endopeptidases belong to the peptidase C56 family, which is classified with the peptidase C26 γ-glutamyl hydrolases (see <PDOC51275>) in the clan PC(C) [E1,E2]. Other peptidase C56 family proteins are structurally and functionally different [2], e.g. human DJ-1 creates a hydrophobic patch at the molecular interface instead of completing the catalytic triad, while E. coli chaperone HSP31 forms a Cys-His-Asp triad.

Some proteins known to contain a PfpI endopeptidase domain:

  • Pyrococcus furiosus intracellular protease 1 (PfpI), an ATP-independent, highly thermically and chemically stable endopeptidase.
  • Pyrococcus horikoshii intracellular protease 1 (PfpI/PH1704).
  • Bacillus subtilis general stress protein 18 (GSP18).
  • Escherichia coli protein yhbO.

The profile we developed covers the entire PfpI endopeptidase domain.


These proteins belong to family C56 in the classification of peptidases [E1,E2].


The PfpI endopeptidase domain profile is in competition with a profile of a related domain, i.e. GATase type 1 (see <PDOC00405>).

Last update:

December 2006 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

PEPTIDASE_C56_PFPI, PS51276; PfpI endopeptidase domain profile  (MATRIX)


1AuthorsDu X. Choi I.-G. Kim R. Wang W. Jancarik J. Yokota H. Kim S.-H.
TitleCrystal structure of an intracellular protease from Pyrococcus horikoshii at 2-A resolution.
SourceProc. Natl. Acad. Sci. U.S.A. 97:14079-14084(2000).
PubMed ID11114201

2AuthorsBandyopadhyay S. Cookson M.R.
TitleEvolutionary and functional relationships within the DJ1 superfamily.
SourceBMC Evol. Biol. 4:6-6(2004).
PubMed ID15070401



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