Active Site

Peptidase S16, active site (IPR008268)

Short name: Peptidase_S16_AS

Description

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [PMID: 7845208]. 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 [PMID: 7845208]. 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 [PMID: 7845208].

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 [PMID: 7845208]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [PMID: 7845208]. 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) [PMID: 7845208, PMID: 8439290].

This signature defines the active site of the serine peptidases belonging to the MEROPS peptidase family S16 (lon protease family, clan SF). These proteases which are dependent on the hydrolysis of ATP for their activity and have a serine in their active site, they include:

  • Bacterial ATP-dependent proteases [PMID: 8294008, PMID: 8331083]. The prototype of those bacterial enzymes is the Escherichia coli La protease (EC:3.4.21.53) (gene lon). La is capable of hydrolysing large proteins; it degrades short-lived regulatory (such as rcsA and sulA) and abnormal proteins. It is a cytoplasmic protein of 87 kDa that associates as an homotetramer. Its proteolytic activity is stimulated by single-stranded DNA.
  • Eukaryotic mitochondrial matrix proteases [PMID: 8276800, PMID: 8248235]. The prototype of these enzymes is the yeast PIM1 protease. It is a mitochondrial matrix protein of 120 kDa that associated as an homohexamer. It catalyses the initial step of mitochondrial protein degradation.
  • Haemophilus influenzae lon-B (HI1324), a protein which does not contain the ATP-binding domain, but possess a slightly divergent form of the catalytic domain.

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004176 ATP-dependent peptidase activity
GO:0004252 serine-type endopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns