Sortase

Sortase family
Sortase "RCSB Protein Data Bank - Structure Summary for 3O0P - Pilus-related Sortase C of Group B Streptococcus". http://www.rcsb.org/pdb/explore/explore.do?structureId=3O0P. 
Identifiers
Symbol Sortase
Pfam PF04203
InterPro IPR005754
SCOP 1ija
Sortase B
Identifiers
Symbol Sortase_B
Pfam PF07170
InterPro IPR009835
SCOP 1qxa
Transmembrane exosortase (Exosortase_EpsH)
Identifiers
Symbol Exosortase_EpsH
Pfam PF09721

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.[1] They act as both proteases and transpeptidases.[2] 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.[3][4]

Contents

Reaction

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.[5][6] and isopeptide bonding 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.[7] 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.[8]

Function

The pili endproducts often make the bacteria more virulent due to adherence to host cells[9] or biofilm[10] 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 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[11] as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.[12]

Structure

This group of cysteine peptidases belong to MEROPS 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.[13]

References

  1. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2544515. 
  2. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2519520. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=33977. 
  7. ^ Kang HJ, Coulibaly F, Proft T, Baker EN (2011). Hofmann, Andreas. 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 3019223. PMID 21264317. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3019223. 
  8. ^ Manzano C, Izoré T, Job V, Di Guilmi AM, Dessen A (November 2009). "Sortase activity is controlled by a flexible lid in the pilus biogenesis mechanism of gram-positive pathogens". Biochemistry 48 (44): 10549–10557. doi:10.1021/bi901261y. PMID 19810750. 
  9. ^ Mandlik A, Swierczynski A, Das A, Ton-That H (January 2008). "Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development". Trends Microbiol. 16 (1): 33–40. doi:10.1016/j.tim.2007.10.010. PMC 2841691. PMID 18083568. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2841691. 
  10. ^ Konto-Ghiorghi Y, Mairey E, Mallet A, Duménil G, Caliot E, Trieu-Cuot P, Dramsi S (May 2009). Gilmore, Michael S.. ed. "Dual role for pilus in adherence to epithelial cells and biofilm formation in Streptococcus agalactiae". PLoS Pathog. 5 (5): e1000422. doi:10.1371/journal.ppat.1000422. PMC 2674936. PMID 19424490. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2674936. 
  11. ^ 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. 
  12. ^ SIGA Technologies (September 2006). "Schedule 14A". U.S. Securities and Exchange Commission. http://www.sec.gov/Archives/edgar/data/1010086/000095013606007825/file1.htm. Retrieved 29 October 2009. 
  13. ^ 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

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