Summary for clan PA

Summary Structure Literature
Clan type peptidaseS01.001 - chymotrypsin A (cattle-type) (Bos taurus), MEROPS Accession MER0000002 (peptidase unit: 34-263); PDB accession 2GMT
HistoryMEROPS 1.202 (17 June 1997)
DescriptionSerine or cysteine nucleophile; catalytic residues in the order His, Asp, Ser (or Cys) in sequence; all endopeptidases
Contents of clanClan PA contains endopeptidases.
EvidenceFamilies are assigned to clan PA on the basis of similar protein folds (see below) or similarly-arranged catalytic residues.
Catalytic mechanismThe clan contains both serine and cysteine peptidases, typically with a catalytic triad like His, Asp/Glu, Cys/Ser (see the Alignments for subclans PA(C) and PA(S)). There is some debate as to whether a catalytic triad (His, Asp/Glu, Cys) or just a dyad (His, Cys) exists in some of the viral cysteine peptidases (e.g. hepatitis A virus picornain 3C (C03.005), in which the side-chain of the Asp points away from the active site (Bergmann et al., 1997). The details of the catalytic mechanism have been reviewed for the cysteine peptidases by Polgar (2004) and for the serine peptidases by Polgar (2004).
Peptidase activityActivity is endopeptidase activity with a wide range of specificities (see individual family summaries). The cysteine endopeptidases (in subclan PA(C)) are polyprotein-processing enzymes of RNA viruses.
Protein foldThe tertiary structure for chymotrypsin (S01.001) was one of the first peptidase structures to be determined (Mathews et al., 1967) and shows two, closed beta barrel domains with the active site between the domains. Because of the resemblance to a motif used in ancient mosaics, each domain is described as a Greek key. The domains are believed to be derived from an ancient gene duplication (Lesk & Fordham, 1996). Although chymotrypsin is described as an 'all-beta protein', there is a C-terminal alpha helix that interacts with both domains and presumably stabilises their interaction. The N-terminal barrel bears two of the active site residues (His and Asp), and the nucleophilic Ser is on the C-terminal barrel.
EvolutionIt is likely that the serine peptidases of clan PA are ancestral, and were acquired by RNA viruses from their hosts. In the viruses, several families of serine peptidase persist, but on one or more occasions the catalytic serine seems to have been replaced by cysteine with retention of activity, and the resulting cysteine peptidases have further diversified.
Homologous non-peptidase familiesThere are non-peptidase proteins in several of the families within clan PA. However, there are as yet no known families of proteins that share this protein fold but contain no peptidases.
Activation mechanismIn family S1, active trypsin (S01.151) is formed from trypsinogen by cleavage of an N-terminal propeptide that permits folding to the active configuration (Huber & Bode, 1978).
Other databases PFAMCL0124
SCOP50494

Families

Family Family Type Peptidase Structure
C03 poliovirus-type picornain 3C (human poliovirus 1) Yes
C04 nuclear-inclusion-a peptidase (plum pox virus) (plum pox virus) Yes
C107 alphamesonivirus 3C-like peptidase (Cavally virus) -
C24 rabbit hemorrhagic disease virus 3C-like peptidase (rabbit hemorrhagic disease virus) -
C30 porcine transmissible gastroenteritis virus-type main peptidase (transmissible gastroenteritis virus) Yes
C37 calicivirin (Southampton virus) Yes
C62 gill-associated virus 3C-like peptidase (gill-associated virus) -
C74 pestivirus NS2 peptidase (bovine viral diarrhea virus 1) -
C99 iflavirus processing peptidase (Ectropis obliqua picorna-like virus) -
S01 chymotrypsin A (cattle-type) (Bos taurus) Yes
S03 togavirin (Sindbis virus) Yes
S06 IgA1-specific serine peptidase ({Neisseria}-type) (Neisseria gonorrhoeae) Yes
S07 flavivirin (yellow fever virus) -
S29 hepacivirin (hepatitis C virus) Yes
S30 potyvirus P1 peptidase (plum pox virus) -
S31 pestivirus NS3 polyprotein peptidase (bovine viral diarrhea virus 1) -
S32 equine arteritis virus serine peptidase (equine arteritis virus) Yes
S39 sobemovirus peptidase (cocksfoot mottle virus) Yes
S46 dipeptidyl-peptidase 7 ({Porphyromonas gingivalis}-type) (Porphyromonas gingivalis) -
S55 SpoIVB peptidase (Bacillus subtilis) -
S64 Ssy5 peptidase (Saccharomyces cerevisiae) -
S65 picornain-like cysteine peptidase (Breda-1 torovirus) (Breda virus) -
S75 White bream virus serine peptidase (White bream virus) -

Distribution of clan PA among Kingdoms of Organisms

FamilyBacteriaArchaeaProtozoaFungiPlantsAnimalsViruses
C3-----++
C4+-----+
C17------+
C24------+
C30------+
C37------+
C62------+
C74------+
C99------+
S1+++++++
S3------+
S6+-----+
S7-----++
S29------+
S30------+
S31-----++
S32------+
S39------+
S46+---+--
S55+------
S64---+---
S65------+
S75------+
Clan+++++++