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119  structures 3118  species 1  interaction 9205  sequences 69  architectures

Family: Sortase (PF04203)

Summary: Sortase domain

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Sortase Edit Wikipedia article

Sortase family
Pilus-related Sortase C of Group B Streptococcus. PDB entry 3O0P[1]
Symbol Sortase
Pfam PF04203
InterPro IPR005754
SCOP 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, followed by 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 cell wall components. 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.[2][3] Although sortase A, the "housekeeping" sortase, typically acts on many protein targets, other forms of sortase recognize variant forms of the cleavage motif, or that catalyze the assembly of pilins into pili.[4][5][6]


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.[7][8]

Biological role

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 and archaeosortase are functionally analogous, while not in any way homologous to sortase[9].

As an antibiotic target

The sortases are thought to be good targets for new antibiotics[10] as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.[11]


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.[12]

Use in structural biology

The transpeptidase activity of sortase is taken advantage of by structural biologists to produce fusion proteins in vitro. The recognition motif (LPXTG) is added to the C-terminus of a protein of interest while an oligo-glycine motif is added to the N-terminus of the second protein to be ligated. Upon addition of sortase to the protein mixture, the two peptides are covalently linked through a native peptide bond. This reaction is employed by NMR spectroscopists to produce NMR invisible solubility tags [13] and in one example by X-ray crystallographers to promote complex formation.[14]

See also


  1. ^ Cozzi, R; Malito, E; Nuccitelli, A; d'Onofrio, M; Martinelli, M; Ferlenghi, I; Grandi, G; Telford, J. L.; Maione, D; Rinaudo, C. D. (2011). "Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus". The FASEB Journal. 25 (6): 1874–86. doi:10.1096/fj.10-174797. PMID 21357525. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Oh S, Budzik J, 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 2544515Freely accessible. PMID 18784365. 
  5. ^ 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 2519520Freely accessible. PMID 18606733. 
  6. ^ Kang HJ, Coulibaly F, Proft T, Baker EN (2011). Hofmann A, ed. "Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly". PLoS ONE. 6 (1): e15969. doi:10.1371/journal.pone.0015969. PMC 3019223Freely accessible. PMID 21264317. 
  7. ^ 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. 
  8. ^ 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 33977Freely accessible. PMID 10805759. 
  9. ^ Haft DH, Payne SH, Selengut JD (2012). "Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification". J Bacteriol. 194 (1): 36–48. doi:10.1128/JB.06026-11. PMC 3256604Freely accessible. PMID 22037399. 
  10. ^ 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. 
  11. ^ SIGA Technologies (September 2006). "Schedule 14A". U.S. Securities and Exchange Commission. Retrieved 29 October 2009. 
  12. ^ 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. 
  13. ^ Kobashigawa Y, Kumeta H, Ogura K, Inagaki F (January 2009). "Attachment of an NMR-invisible solubility enhancememnt tag using a sortase mediated protein ligation method". Journal of Biomolecular NMR. 43 (3): 145–150. doi:10.1007/s10858-008-9296-5. PMID 19140010. 
  14. ^ Wang Y, Pascoe HG, Brautigam CA, He H, Zhang X (October 2013). "Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin". eLIFE. 2: e01279. doi:10.7554/eLife.01279. PMC 3787391Freely accessible. PMID 24137545. 

Further reading

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 domain 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

This family includes Staphylococcus aureus sortase, a transpeptidase that attaches surface proteins by the Thr of an LPXTG motif to the cell wall. It also includes a protein required for correct assembly of an LPXTG-containing fimbrial protein, a set of homologous proteins from Streptococcus pneumoniae, in which LPXTG proteins are common. However, related proteins are found in Bacillus subtilis and Methanobacterium thermoautotrophicum, in which LPXTG-mediated cell wall attachment is not known [PUBMED:10427003].

Sortase refers to a group of prokaryotic enzymes which catalyze the assembly of pilins into pili, and the anchoring of pili to the cell wall [PUBMED:2544515]. They act as both proteases and transpeptidases [PUBMED:2519520]. Sortase, a transpeptidase present in almost all Gram-positive bacteria, anchors a range of important surface proteins to the cell wall [PUBMED:11401711, PUBMED:14572546]. The sortases are thought to be good targets for new antibiotics as they are important proteins for pathogenic bacteria [PUBMED:18321961].

Domain organisation

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Curation and family details

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Seed source: TIGRFAMs (release 2.0);
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: TIGRFAMs, Finn RD
Number in seed: 86
Number in full: 9205
Average length of the domain: 137.30 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 52.22 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.6 26.6
Trusted cut-off 26.6 26.6
Noise cut-off 26.5 26.5
Model length: 125
Family (HMM) version: 13
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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 119 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 sequence.

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