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.