Subtilase
Encyclopedia
Subtilases are a family
of subtilisin
-like serine protease
s. They appear to have independently and convergently evolved an Asp/Ser
/His
catalytic triad
, like in the trypsin serine proteases
. The structure of proteins in this family shows that they have an alpha/beta fold containing a 7-stranded parallel beta sheet
.
The subtilisin family is the second largest serine protease family characterised to date. Over 200 subtilises are presently known, more than 170 of which with their complete amino acid sequence. Subtilase is widespread, being found in eubacteria, archaebacteria, eukaryotes and viruses. The vast majority of the family are endopeptidase
s, although there is an exopeptidase
, tripeptidyl peptidase
. Structures have been determined for several members of the subtilisin family showing that subtilisins exploit the same catalytic triad as the chymotrypsin
s although the residues occur in a different order (His/Asp/Ser in chymotrypsin and Asp/His/Ser in subtilisin); otherwise the structures show similarity to no other proteins. Some subtilisins are mosaic proteins, whereas others contain N- and C-terminal extensions that show no sequence similarity to any other known protein. Based on sequence homology, a subdivision into six families has been proposed.
The proprotein-processing endopeptidases kexin
, furin
and related enzymes form a distinct subfamily known as the kexin subfamily (S8B). These preferentially cleave C-terminally to paired basic amino acids. Members of this subfamily can be identified by subtly different motifs around the active site. Members of the kexin family, along with endopeptidases R, T and K from the yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require thiol activation. This can be attributed to the presence of Cys-173 near to the active histidine.Only 1 viral member of the subtilisin family is known, a 56-kDa protease from herpes virus 1, which infects the channel catfish.
Sedolisins (serine-carboxyl peptidases) are proteolytic enzymes whose fold resembles that of subtilisin; however, they are considerably larger, with the mature catalytic domains containing approximately 375 amino acids. The defining features of these enzymes are a unique catalytic triad, Ser/Glu/Asp, as well as the presence of an aspartic acid residue in the oxyanion hole. High-resolution crystal structures have now been solved for sedolisin from Pseudomonas sp. 101, as well as for kumamolisin from a thermophilic bacterium, Bacillus novo sp. MN-32. Mutations in the human gene leads to a fatal neurodegenerative disease.
; MBTPS1; PCSK1; PCSK2; PCSK4
; PCSK5
; PCSK6
; PCSK7
;
PCSK9
; TPP2
;
Protein family
A protein family is a group of evolutionarily-related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....
of subtilisin
Subtilisin
Subtilisin is a non-specific protease initially obtained from Bacillus subtilis.Subtilisins belong to subtilases, a group of serine proteases that initiate the nucleophilic attack on the peptide bond through a serine residue at the active site. They are physically and chemically...
-like serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
s. They appear to have independently and convergently evolved an Asp/Ser
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
/His
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
catalytic triad
Catalytic triad
A catalytic triad refers to the three amino acid residues found inside the active site of certain protease enzymes: serine , aspartate , and histidine . They work together to break peptide bonds on polypeptides. In general terms, catalytic triad can refer to any set of three residues that function...
, like in the trypsin serine proteases
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
. The structure of proteins in this family shows that they have an alpha/beta fold containing a 7-stranded parallel beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
.
The subtilisin family is the second largest serine protease family characterised to date. Over 200 subtilises are presently known, more than 170 of which with their complete amino acid sequence. Subtilase is widespread, being found in eubacteria, archaebacteria, eukaryotes and viruses. The vast majority of the family are endopeptidase
Endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...
s, although there is an exopeptidase
Exopeptidase
An exopeptidase is an enzyme produced in the pancreas that catalyses the removal of an amino acid from the end of a polypeptide chain. Exopeptidase cleaves the end of a polypeptide chain....
, tripeptidyl peptidase
Tripeptidyl peptidase
A tripeptidyl peptidase is a type of enzyme.Types include:* Tripeptidyl peptidase I* Tripeptidyl peptidase II...
. Structures have been determined for several members of the subtilisin family showing that subtilisins exploit the same catalytic triad as the chymotrypsin
Chymotrypsin
Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...
s although the residues occur in a different order (His/Asp/Ser in chymotrypsin and Asp/His/Ser in subtilisin); otherwise the structures show similarity to no other proteins. Some subtilisins are mosaic proteins, whereas others contain N- and C-terminal extensions that show no sequence similarity to any other known protein. Based on sequence homology, a subdivision into six families has been proposed.
The proprotein-processing endopeptidases kexin
Kexin
Kexin is a prohormone processing protease found in the budding yeast that shares structural similarities with the bacterial protease subtilisin. It is encoded by the yeast gene KEX2 and usually referred to in the scientific community as Kex2p. The first mammalian homologue of this protein to be...
, furin
Furin
Furin is a protein that in humans is encoded by the FURIN gene. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR and therefore the protein was named furin...
and related enzymes form a distinct subfamily known as the kexin subfamily (S8B). These preferentially cleave C-terminally to paired basic amino acids. Members of this subfamily can be identified by subtly different motifs around the active site. Members of the kexin family, along with endopeptidases R, T and K from the yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require thiol activation. This can be attributed to the presence of Cys-173 near to the active histidine.Only 1 viral member of the subtilisin family is known, a 56-kDa protease from herpes virus 1, which infects the channel catfish.
Sedolisins (serine-carboxyl peptidases) are proteolytic enzymes whose fold resembles that of subtilisin; however, they are considerably larger, with the mature catalytic domains containing approximately 375 amino acids. The defining features of these enzymes are a unique catalytic triad, Ser/Glu/Asp, as well as the presence of an aspartic acid residue in the oxyanion hole. High-resolution crystal structures have now been solved for sedolisin from Pseudomonas sp. 101, as well as for kumamolisin from a thermophilic bacterium, Bacillus novo sp. MN-32. Mutations in the human gene leads to a fatal neurodegenerative disease.
Human proteins containing this domain
FURINFurin
Furin is a protein that in humans is encoded by the FURIN gene. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR and therefore the protein was named furin...
; MBTPS1; PCSK1; PCSK2; PCSK4
PCSK4
Proprotein convertase subtilisin/kexin type 4 is an enzyme that in humans is encoded by the PCSK4 gene.-Further reading:...
; PCSK5
PCSK5
Proprotein convertase subtilisin/kexin type 5 is an enzyme that in humans is encoded by the PCSK5 gene.-Further reading:...
; PCSK6
PCSK6
Proprotein convertase subtilisin/kexin type 6 is an enzyme that in humans is encoded by the PCSK6 gene.-Further reading:...
; PCSK7
PCSK7
Proprotein convertase subtilisin/kexin type 7 is an enzyme that in humans is encoded by the PCSK7 gene.-Further reading:...
;
PCSK9
PCSK9
Proprotein convertase subtilisin/kexin type 9, also known as PCSK9, is an enzyme which in humans is encoded by the PCSK9 gene with orthologs found across many species.- Function :...
; TPP2
TPP2
Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the TPP2 gene.. Among other things it is heavily implicated in MHC class-I processing, as it has both endopeptidase and exopeptidase activity.-External links:...
;