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74  structures 1737  species 1  interaction 4873  sequences 19  architectures

Family: Sortase (PF04203)

Summary: Sortase family

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This is the Wikipedia entry entitled "Sortase". More...

Sortase Edit Wikipedia article

Sortase family
Sortase.png
Identifiers
Symbol Sortase
Pfam PF04203
InterPro IPR005754
SCOP 1ija
SUPERFAMILY 1ija
OPM superfamily 359
OPM protein 1rz2

Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, then a cluster of basic residues such as arginine. Cleavage occurs between the Thr and Gly, with transient attachment through the Thr residue to the active site Cys residue, followed by transpeptidation that attaches the protein covalently to the cell wall. Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative (e.g. Shewanella putrefaciens) or Archaea (e.g. Methanobacterium thermoautotrophicum), where cell wall LPXTG-mediated decoration has not been reported.[1][2] Although sortase A, the "housekeeping" sortase, typically acts on many targets per genome, other forms of sortase occur that recognize variant forms of the cleavage motif, or that catalyze the assembly of pilins into pili. [3] [4] [5]

Reaction[edit]

The Staphylococcus aureus 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.[6][7]

Biological role[edit]

Substrate proteins attached to cell walls by sortases include enzymes, pilins, and adhesion-mediating large surface glycoproteins. These proteins often play important roles in virulence, infection, and colonization by pathogens.

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.

Note that exosortase is functionally analogous, but not in any way homologous to sortase.

As an antibiotic target[edit]

The sortases are thought to be good targets for new antibiotics[8] as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.[9]

Structure[edit]

This group of cysteine peptidases belong to MEROPS peptidase family C60 (clan C-) and include the members of several subfamilies of sortases.

Another sub-family of sortases (C60B in MEROPS) contains bacterial sortase B proteins that are approximately 200 residues long.[10]

References[edit]

  1. ^ Schneewind O, Mazmanian SK, Ton-that H (2001). "Sortase-catalysed anchoring of surface proteins to the cell wall of Staphylococcus aureus". Mol. Microbiol. 40 (5): 1049–1057. doi:10.1046/j.1365-2958.2001.02411.x. PMID 11401711. 
  2. ^ Pallen MJ, Henderson IR, Chaudhuri RR (2003). "Genomic analysis of secretion systems". Curr Opin Microbiol 6 (5): 519–527. doi:10.1016/j.mib.2003.09.005. PMID 14572546. 
  3. ^ Oh S, Budzik J, and Schneewind O (September 2008). "Sortases make pili from three ingredients". Proc Natl Acad Sci U S A. 105 (37): 13703–13704. doi:10.1073/pnas.0807334105. PMC 2544515. PMID 18784365. 
  4. ^ LeMieux J, Woody S, Camilli A (September 2008). "Roles of the sortases of Streptococcus pneumoniae in assembly of the RlrA pilus". J. Bacteriol. 190 (17): 6002–6013. doi:10.1128/JB.00379-08. PMC 2519520. PMID 18606733. 
  5. ^ Kang HJ, Coulibaly F, Proft T, Baker EN (2011). "Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly". In Hofmann, Andreas. PLoS ONE 6 (1): e15969. doi:10.1371/journal.pone.0015969. PMC 3019223. PMID 21264317. 
  6. ^ Mazmanian SK, Liu G, Ton-That H, Schneewind O (July 1999). "Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall". Science 285 (5428): 760–3. doi:10.1126/science.285.5428.760. PMID 10427003. 
  7. ^ Cossart P, Jonquières R (May 2000). "Sortase, a universal target for therapeutic agents against gram-positive bacteria?". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5013–5. doi:10.1073/pnas.97.10.5013. PMC 33977. PMID 10805759. 
  8. ^ Maresso AW, Schneewind O (March 2008). "Sortase as a target of anti-infective therapy". Pharmacol. Rev. 60 (1): 128–141. doi:10.1124/pr.107.07110. PMID 18321961. 
  9. ^ SIGA Technologies (September 2006). "Schedule 14A". U.S. Securities and Exchange Commission. Retrieved 29 October 2009. 
  10. ^ Pallen MJ, Lam AC, Antonio M, Dunbar K (March 2001). "An embarrassment of sortases - a richness of substrates?". Trends Microbiol. 9 (3): 97–102. doi:10.1016/S0966-842X(01)01956-4. PMID 11239768. 

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR005754

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Sortase family Provide feedback

The founder member of this family is S.aureus sortase, a transpeptidase that attaches surface proteins by the threonine of an LPXTG motif to the cell wall [1].

Literature references

  1. Mazmanian SK, Liu G, Ton-That H, Schneewind O; , Science 1999;285:760-763.: Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. PUBMED:10427003 EPMC:10427003

  2. Pallen MJ, Lam AC, Antonio M, Dunbar K; , Trends Microbiol 2001;9:97-102.: An embarrassment of sortases - a richness of substrates? PUBMED:11239768 EPMC:11239768


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005754

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.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad [PUBMED:11517925].

This group of cysteine peptidases belong to MEROPS peptidase family C60 (clan C-) and include the members of both subfamilies of sortases. The Staphylococcus aureus 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 [PUBMED:10427003]. 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 [PUBMED:11401711, PUBMED:14572546].

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.

Domain organisation

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(138)
Full
(4873)
Representative proteomes NCBI
(3560)
Meta
(293)
RP15
(283)
RP35
(543)
RP55
(695)
RP75
(783)
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Format an alignment

  Seed
(138)
Full
(4873)
Representative proteomes NCBI
(3560)
Meta
(293)
RP15
(283)
RP35
(543)
RP55
(695)
RP75
(783)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(138)
Full
(4873)
Representative proteomes NCBI
(3560)
Meta
(293)
RP15
(283)
RP35
(543)
RP55
(695)
RP75
(783)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: TIGRFAMs (release 2.0);
Previous IDs: none
Type: Family
Author: TIGRFAMs, Finn RD
Number in seed: 138
Number in full: 4873
Average length of the domain: 135.30 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 51.42 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.3 21.3
Noise cut-off 21.1 21.2
Model length: 128
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Sortase

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Sortase domain has been found. There are 74 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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