| Clan type peptidase | S01.001 - chymotrypsin A (cattle-type) (Bos taurus), MEROPS Accession MER0000002 (peptidase unit: 34-263); PDB accession 2GMT |
| History | MEROPS 1.202 (17 June 1997) |
| Description | Serine or cysteine nucleophile; catalytic residues in the order His, Asp, Ser (or Cys) in sequence; all endopeptidases |
| Contents of clan | Clan PA contains endopeptidases. |
| Evidence | Families are assigned to clan PA on the basis of similar protein folds (see below) or similarly-arranged catalytic residues. |
| Catalytic mechanism | The 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 activity | Activity 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 fold | The 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. |
| Evolution | It 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viruses, several families of serine peptidase persist, but on one or more occasions the catalytic serine seems to have been replaced by cysteine with retention of activity, and the resulting cysteine peptidases have further diversified.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 families | There 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 mechanism | In 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). |
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Other databases
| PFAM | CL0124 |
|
| SCOP | 50494 |
| 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) |
- |
| C125 |
protease (sacbrood virus) (Sacbrood 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 serine peptidase (Breda-1 torovirus) (Breda virus) |
- |
| S75 |
White bream virus serine peptidase (White bream virus) |
- |
