Sortase
Encyclopedia
Sortase refers to a group of prokaryotic
enzyme
s which catalyze the assembly of pilin
s into pili
, and the anchoring of pili to the cell wall. They act as both protease
s and transpeptidase
s. Sortase, a transpeptidase present in almost all Gram-positive bacteria, anchors a range of important surface proteins to the cell wall. Sortase homologues are found in almost all Gram-positives, a single Gram-negative (Shewanella putrefaciens
) and an archaean (Methanobacterium thermoautotrophicum
), where cell wall LPXTG-mediated decoration has not been reported.
sortase is a transpeptidase that attaches surface proteins to the cell wall; it cleaves between the Gly and Thr of the LPXTG motif and catalyses the formation of an amide bond between the carboxyl-group of threonine and the amino-group of the cell-wall peptidoglycan. and isopeptide bond
ing may occur between various side chains such as those of Lys
and Asn
.
Sortase performs two main tasks that are involved with pilus assembly. They consist of some sortase enzymes focusing on attaching proteins to cell walls, while other sortase enzymes focus on "housekeeping" roles. Sortase enzymes mediate the covalent attachment of substrate proteins to cell walls, which plays a crucial role in virulence, infection, and colonization by pathogens.
To determine the role in pilus assembly, pilus expression and cell wall anchoring were analyzed in studies with sortaseA deletion mutants. When sortaseA was not present the pilus polymerization was not affected, but pilus expression and cell wall anchoring was reduced and pili accumulated in the culture supernatant. This study proves that sortaseA is involved in covalent anchoring of pili to the cell wall.
Surface proteins not only promote interaction between the invading pathogen and animal tissues, but also provide ingenious strategies for bacterial escape from the host's immune response. In the case of S. aureus
protein A, immunoglobulins are captured on the microbial surface and camouflage bacteria during the invasion of host tissues. S. aureus mutants lacking the srtA gene fail to anchor and display some surface proteins and are impaired in the ability to cause animal infections. Sortase acts on surface proteins that are initiated into the secretion (Sec) pathway and have their signal peptide removed by signal peptidase. The S. aureus genome encodes two sets of sortase and secretion genes. It is conceivable that S. aureus has evolved more than one pathway for the transport of 20 surface proteins to the cell wall envelope.
peptidase family C60 (clan C-) and include the members of both subfamilies of sortases.
Another sub-family of sortases (C60B in MEROPS) contains bacterial sortase B proteins that are approximately 200 residues long.
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s which catalyze the assembly of pilin
Pilin
Pilin refers to a class of fibrous proteins that are found in pilus structures in bacteria. Bacterial pili are used in the exchange of genetic material during bacterial conjugation, and a short pilus called a fimbrium is used as a cell adhesion mechanism. Although not all bacteria have pili or...
s into pili
Pilus
right|thumb|350px|Schematic drawing of bacterial conjugation. 1- Donor cell produces pilus. 2- Pilus attaches to recipient cell, brings the two cells together. 3- The mobile plasmid is nicked and a single strand of DNA is then transferred to the recipient cell...
, and the anchoring of pili to the cell wall. They act as both protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s and transpeptidase
Transpeptidase
A transpeptidase is a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls. This enzyme is also known by several other names including DD-peptidase, DD-transpeptidase, D-alanyl-D-alanine carboxypeptidase and serine-type D-Ala-D-Ala carboxypeptidase...
s. Sortase, a transpeptidase present in almost all Gram-positive bacteria, anchors a range of important surface proteins to the cell wall. Sortase homologues are found in almost all Gram-positives, a single Gram-negative (Shewanella putrefaciens
Shewanella putrefaciens
Shewanella putrefaciens is a Gram-negative bacterium. It has been isolated from marine environments, as well as from anaerobic sandstone in the Morrison formation in New Mexico. S...
) and an archaean (Methanobacterium thermoautotrophicum
Methanobacterium
In taxonomy, Methanobacterium is a genus of the Methanobacteriaceae.- External links :...
), where cell wall LPXTG-mediated decoration has not been reported.
Reaction
The Staphylococcus aureusStaphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
sortase is a transpeptidase that attaches surface proteins to the cell wall; it cleaves between the Gly and Thr of the LPXTG motif and catalyses the formation of an amide bond between the carboxyl-group of threonine and the amino-group of the cell-wall peptidoglycan. and isopeptide bond
Isopeptide bond
An isopeptide bond is an amide bond that is not present on the main chain of a protein. The bond forms between the carboxyl terminus of one protein and the amino group of a lysine residue on another protein....
ing may occur between various side chains such as those of Lys
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and Asn
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
.
Sortase performs two main tasks that are involved with pilus assembly. They consist of some sortase enzymes focusing on attaching proteins to cell walls, while other sortase enzymes focus on "housekeeping" roles. Sortase enzymes mediate the covalent attachment of substrate proteins to cell walls, which plays a crucial role in virulence, infection, and colonization by pathogens.
To determine the role in pilus assembly, pilus expression and cell wall anchoring were analyzed in studies with sortaseA deletion mutants. When sortaseA was not present the pilus polymerization was not affected, but pilus expression and cell wall anchoring was reduced and pili accumulated in the culture supernatant. This study proves that sortaseA is involved in covalent anchoring of pili to the cell wall.
Function
The pili endproducts often make the bacteria more virulent due to adherence to host cells or biofilm formation.Surface proteins not only promote interaction between the invading pathogen and animal tissues, but also provide ingenious strategies for bacterial escape from the host's immune response. In the case of S. aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
protein A, immunoglobulins are captured on the microbial surface and camouflage bacteria during the invasion of host tissues. S. aureus mutants lacking the srtA gene fail to anchor and display some surface proteins and are impaired in the ability to cause animal infections. Sortase acts on surface proteins that are initiated into the secretion (Sec) pathway and have their signal peptide removed by signal peptidase. The S. aureus genome encodes two sets of sortase and secretion genes. It is conceivable that S. aureus has evolved more than one pathway for the transport of 20 surface proteins to the cell wall envelope.
As an antibiotic target
The sortases are thought to be good targets for new antibiotics as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.Structure
This group of cysteine peptidases belong to MEROPSMerops
Merops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
peptidase family C60 (clan C-) and include the members of both subfamilies of sortases.
Another sub-family of sortases (C60B in MEROPS) contains bacterial sortase B proteins that are approximately 200 residues long.