1887

Chapter 7 : Sortase Pathways in Gram-Positive Bacteria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Sortase Pathways in Gram-Positive Bacteria, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818395/9781555813017_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555818395/9781555813017_Chap07-2.gif

Abstract:

Research within the past decade has revealed that a large fraction of bacterial surface proteins are covalently anchored to the cell wall by the action of sortase enzymes, in a universally conserved process that is important for infectivity. This chapter presents a review of the structural basis of sortase-mediated cell wall anchoring, drawing on recent structural, biochemical, and bioinformatic studies of this enzyme family. In addition to embedding proteins into the underlying membrane (e.g., membrane proteins and lipoproteins), gram-positive bacteria have developed several methods to display surface proteins, each with its own distinctive structural features. It has long been known that some proteins in gram-positive bacteria are covalently linked to the cell wall, but the enzymes that place them there have only recently been identified. SrtA-related proteins were found in nearly all gram-positive bacteria with sequenced genomes and, in several cases, were demonstrated to be key determinants of infectivity. The broad distribution of sortases in pathogenic bacteria and the essential roles of sortase-anchored surface proteins in the establishment of infection suggest that sortase inhibitors may prove to be effective anti-infective agents. The design of effective sortase inhibitors will require an understanding of the structural biology of sortase-substrate recognition, as well as intimate knowledge of the potentially diverse sortase anchoring pathways and their role in the establishment of infection.

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7

Key Concept Ranking

Bacterial Proteins
0.5411585
Ionization Mass Spectrometry
0.43930244
Cell Wall Components
0.43573672
Cell Wall Proteins
0.43441403
0.5411585
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Mechanisms of cell wall attachment. Choline-binding proteins recognize choline-substituted TA and LTA (asterisks) through 20-residue C-terminal repeats, which form stacked β-hairpins. LTA can be directly bound by the GW domains of InlB. Crystalline S-layer proteins self-assemble at the cell surface; they are tethered to TUA polymers through SLH domains. The SLH domain of ScaC affixes it to the membrane, and its three cohesin domains serve as attachment points for the adaptor proteins and enzymes of the cellulosome. Covalent linkage of Cws-containing proteins by a sortase enzyme produces an amide linkage between the threonine of the LPXTG motif of the sorting signal and the peptide cell wall crossbridge. Adapted from .

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

(A) Schematic of a sortase substrate. The protein is composed of an N-terminal signal peptide and a C-terminal Cws. The Cws contains a conserved LPXTG motif followed by a hydrophobic stretch of amino acids and positively charged residues at the C terminus. (B) Proposed model for the cell wall sorting reaction. The full-length surface protein precursor is secreted through the membrane via an N-terminal signal sequence. A charged tail at the C terminus of the protein may serve as a stop transfer signal. Following cleavage of this secretion signal, a sortase enzyme cleaves the protein between the threonine and glycine residues of the LPXTG motif, forming a thioacyl-enzyme intermediate. The free amine of the cell wall crossbridge of lipid II is deprotonated in the SrtA active site and serves as the acceptor for the transpeptidation reaction. The covalently linked proteinlipid II intermediate may then serve as a substrate for the transglycosylation reaction of cell wall synthesis.

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

(A) Diagram showing the structure of the second substrate of SrtA, lipid II [undecaprenyl-pyrophosphate-MurNAc(-l-Ala–d-iGln–l-Lys(NH-Gly)–d-Ala-d-Ala)-β1→4-GlcNAc)]. The peptide of MurNAc is “branched” by forming a peptide bond between the ε-amine of lysine and a pentaglycine peptide. The terminal glycine α- amine serves as a nucleophile and forms a peptide bond to the carbonyl carbon of the threonine residue within the LPXTG motif. (B) Structure of the cell wall crossbridge. In a 4→3 linkage, a diamino acid (DA; either l-Lys or -Dpm) at position 3 is linked through a peptide bond to the carboxyl of the d-Ala in the position 4 of a neighboring glycan chain, releasing the terminal d-Ala (position 5). These reactions are performed by cell wall transpeptidases (PBPs). The chemical nature of the diamino acid and crossbridge peptides can vary among different bacteria. (C) Cell wall crossbridges of different bacterial strains. In , bacilli, and corynebacteria, the cell wall peptides are unbranched and the diamino acid -Dpm is directly linked to the d-Ala of the neighboring glycan chain.

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Comparison of the primary and tertiary structures of SrtA and SrtB from . (A) Ribbon diagrams of the folds of SrtA (PDB ID, 1IJA; residues 60 to 206) ( ) and SrtB (PDB ID, 1NG5; residues 35 to 244) (Zhang et al., submitted). Both are presented in a similar orientation. The β-barrels of both structures align with a root mean square deviation of 3.2 Å. (B) Sequence alignment of SrtA and SrtB. Similar residues are shaded gray, and the catalytic cysteine and histidine residues are shaded black. Secondary-structure elements are indicated by arrows and cylinders for β-strands and α-helices, respectively. The N termini of both proteins (residues 1 to 59 in SrtA and 1 to 34 in SrtB) are absent in their respective structures and most probably contain a membrane anchor.

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

(A) Ribbon drawing of the structure of SrtA (residues 60 to 206 of the SrtA protein). Beginning at the N terminus, the β1 strand (G74 to I78) is followed by a short hairpin and lies antiparallel to the β2 strand (I83 to Y88). The β2 and β3 strands (V101 to A104) are positioned in parallel and are tethered by a 3 helix (P94 to L97), which crosses over the surface of the enzyme to form the lateral wall of the active site. The β3 and β4 strands (Q113 to G119) lie antiparallel with respect to one another and are followed by a long loop and a second α-helix, which assume a circuitous path to position the β5 strand (S140 to V146) for antiparallel alignment with the β1 strand. The β6 strand (E149 to K155) is then connected by a short hairpin turn for antiparallel pairing and followed by a long loop structure to connect it to the β7 strand (K177 to T183), which is aligned in parallel with β4. The active site sulfhydryl, C184, is positioned at the end of the β7 strand, which includes the LITC signature sequence of sortase enzymes. The structure is completed by a loop (D185 to W194), which connects the β7 and β8 strands (E195 to F200) for antiparallel pairing. Three acidic side chains (E105, E108, and D112) are poised to bind calcium, as judged by localized large-amplitude calcium-dependent changes in their chemical shifts and in surrounding amino acids. Additional residues in the β6-β7 loop displayed calcium-dependent chemical shift changes and may constitute a weaker Ca-binding site (spheres). The active-site side chains of H120, C184, and W194 are shown for reference. (B) Expanded view of the active site. H120 and C184 in sortase form a catalytic dyad that mediates the transpeptidation reaction and are positioned within a large hydrophobic pocket suitable for sorting-signal binding. A tryptophan (W194) is positioned in the active site and may play a limited role in catalysis ( ).

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Proposed chemical mechanism of the SrtA sortase. Like the cysteine protease papain, catalysis presumably proceeds through the formation of a thioacyl intermediate. As the LPXTG substrate enters the active site-pocket, H120 functions as a general base, withdrawing a proton from C184 (step 1). The C184 nucleophile attacks the carbonyl carbon of threonine, and, proceeding through a tetrahedral intermediate (TH1) (step 2), results in a thioacyl-enzyme intermediate (step 3). The N-terminal amine of the pentaglycine crossbridge of lipid II then enters the active-site pocket (step 4), serving as an acceptor for the acyl-enzyme intermediate. Deacylation proceeds through a second tetrahedral intermediate (TH2) (step 5), resulting in the formation of a new peptide bond between the threonine of the LPXTG substrate and the terminal glycine of lipid II (step 6).

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

(A) The position-specific frequency of amino acids within the predicted sorting signals of sortases from different subfamilies. The one-letter symbol for the amino acid residue is given for each position in the six-residue motif. The size of each letter is proportional to the frequency with which an amino acid occurs in each position of the sorting-signal motif in the set of Cws-containing proteins that are predicted to be processed by a particular sortase type. If an amino acid appears in fewer than 8% of the substrates, the letter does not appear in the figure. A single amino acid at any position indicates >92% conservation. When no amino acid type is predominant in a given position of the motif, then the amino acid types found in the motif are given in brackets. (B) Pie chart showing the distribution of sortase homologs in gram-positive bacteria. A total of 176 sortase homologs were identified in gram-positive bacteria: 42 SrtA, 17 SrtB, 54 subfamily 3, 13 subfamily 4, and 14 subfamily 5 sortases. The remaining sortases could not be readily classified into a particular subfamily. (C) Pie chart showing the fraction of the 892 Cws-containing proteins that are predicted to be anchored by different types of sortases. A total of 203 Cws-containing proteins were not assigned to a specific sortase.

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8
Figure 8

Molecular structures of sortase inhibitors. (A to C) structures that contain the LPXTG substrate mimic but replace the labile T-G peptide bond with a diazomethane (A), chloromethane (B), or vinyl sulfone (C) group for irreversible modification of the C184 nucleophile. (D) The phosphinate octapeptide NH-ALPEAΨ(POHCH)GEE-OH is a transition state mimic of the T-G scissile bond. (E) The natural SrtA inhibitor β-sitosterol-3--glucopyransoside from bulbs of .

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818395.chap7
1. Altschul, S. F.,, T. L. Madden,, A. A. Schäffer,, J. Zhang,, Z. Zhang,, W. Miller,, and D. J. Lipman. 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25: 3389 3402.
2. Andrade, M. A.,, F. D. Ciccarelli,, C. Perez-Iratxeta,, and P. Bork. 2002. NEAT: a domain duplicated in genes near the components of a putative Fe 3+ siderophore transporter from Gram-positive pathogenic bacteria. Genome Biol. 3: research0047.1 0047.5.
3. Bae, T.,, and O. Schneewind. 2003. The YSIRK-G/S motif of staphylococcal protein A and its role in efficiency of signal peptide processing. J. Bacteriol. 185: 2910 2919.
4. Barnett, T. C.,, and J. R. Scott. 2002. Differential recognition of surface proteins in Streptococcus pyogenes by two sortase gene homologs. J. Bacteriol. 184: 2181 2191.
5. Barrett, A. J.,, and N. D. Rawlings. 2001. Evolutionary lines of cysteine peptidases. Biol. Chem. Hoppe-Seyler 382: 727 733.
6. Bierne, H.,, S. K. Mazmanian,, M. Trost,, M. G. Pucciarelli,, G. Liu,, P. Dehoux,, L. Jansch,, F. Garcia-del Portillo,, O. Schneewind,, and P. Cossart. 2002. Inactivation of the srtA gene in Listeria monocytogenes inhibits anchoring of surface proteins and affects virulence. Mol. Microbiol. 43: 869 881.
7. Bolken, T. C.,, C. A. Franke,, K. F. Jones,, G. O. Zeller,, C. H. Jones,, E. K. Dutton,, and D. E. Hruby. 2001. Inactivation of the srtA gene in Streptococcus gordonii inhibits cell wall anchoring of surface proteins and decreases in vitro and in vivo adhesion. Infect. Immun. 69: 75 80.
8. Braun, L.,, S. Dramsi,, P. Dehoux,, H. Bierne,, G. Lindahl,, and P. Cossart. 1997. InlB: an invasion protein of Listeria monocytogenes with a novel type of surface association. Mol. Microbiol. 25: 285 294.
9. Bromme, D.,, J. L. Klaus,, K. Okamoto,, D. Rasnick,, and J. T. Palmer. 1996. Peptidyl vinyl sulphones—a new class of potent and selective cysteine protease inhibitors—S2p2 specificity of human cathepsin O2 in comparison with cathepsins S and L. Biochem. J. 315: 85 89.
10. Cabanes, D.,, P. Dehoux,, O. Dussurget,, L. Frangeul,, and P. Cossart. 2002. Surface proteins and the pathogenic potential of Listeria monocytogenes. Trends Microbiol. 10: 238 245.
11. Comfort, D.,, and R. T. Clubb. 2004. A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria. Infect. Immun. 72: 2710 2722.
12. Connolly, K. M.,, B. T. Smith,, R. Pilpa,, U. Ilangovan,, M. E. Jung,, and R. T. Clubb. 2003. Sortase from Staphylococcus aureus does not contain a thiolate-imidazolium ion pair in its active site. J. Biol. Chem. 278: 34061 34065.
13. Cossart, P.,, and R. Jonquieres. 2000. Sortase, a universal target for therapeutic agents against Gram-positive bacteria? Proc. Nat. Acad. Sci. USA 97: 5013 5015.
14. Drenth, J.,, J. N. Jansonius,, R. Koekoek,, H. M. Swen,, and B. G. Wolthers. 1968. Structure of papain. Nature 218: 929 932.
15. Eddy, S. R. 1998. Profile hidden Markov models. Bioinformatics 14: 755 763.
16. Engelhardt, H.,, and J. Peters. 1998. Structural research on surface layers: a focus on stability, surface layer homology domains, and surface layer-cell wall interactions. J. Struct. Biol. 124: 276 302.
17. Fernandez-Tornero, C.,, R. Lopez,, E. Garcia,, G. Gimenez-Gallego,, and A. Romero. 2001. A novel solenoid fold in the cell wall anchoring domain of the pneumococcal virulence factor LytA. Nat. Struct. Biol. 8: 1020 1024.
18. Filipe, S. R.,, E. Severina,, and A. Tomasz. 2001. Functional analysis of Streptococcus pneumoniae MurM reveals the region responsible for its specificity in the synthesis of branched cell wall peptides. J. Biol. Chem. 276: 39618 39628.
19. Fischetti, V. A.,, K. F. Jones,, and J. R. Scott. 1985. Size variation of the M protein in group A streptococci. J. Exp. Med. 161: 1384 1401.
20. Fischetti, V. A.,, V. Pancholi,, and O. Schneewind. 1990. Conservation of a hexapeptide sequence in the anchor region of surface proteins from gram-positive cocci. Mol. Microbiol. 4: 1603 1605.
21. Fischetti, V. A.,, V. Pancholi,, and O. Schneewind,. 1991. Common characteristics of the surface proteins from gram-positive cocci, p. 290 294. In G. M. Dunny,, P. P. Cleary,, and L. L. Mckay (ed.), Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci: Third International ASM Conference. American Society for Microbiology, Washington, D.C.
22. Garandeau, C.,, H. Reglier-Poupet,, I. Dubail,, J. L. Beretti,, P. Berche,, and A. Charbit. 2002. The sortase SrtA of Listeria monocytogenes is involved in processing of internalin and in virulence. Infect. Immun. 70: 1382 1390.
23. Goffin, C.,, and J. M. Ghuysen. 2002. Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent. Microbiol. Mol. Biol. Rev. 66: 702 738.
24. Hava, D. L.,, and A. Camilli. 2002. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45: 1389 1406.
25. Hava, D. L.,, C. J. Hemsley,, and A. Camilli. 2003. Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA. J. Bacteriol. 185: 413 421.
26. Higashi, Y.,, J. L. Strominger,, and C. C. Sweeley. 1967. Structure of a lipid intermediate in cell wall peptidoglycan synthesis: a derivative of a C55 isoprenoid alcohol. Proc. Nat. Acad. Sci. USA 57: 1878 1884.
27. Higashi, Y.,, J. L. Strominger,, and C. C. Sweeley. 1970. Biosynthesis of the peptidoglycan of bacterial cell walls. XXI. Isolation of free C55-isoprenoid alcohol and of lipid intermediates in peptidoglycan synthesis from Staphylococcus aureus. J. Biol. Chem. 245: 3697 3702.
28. Huang, X.,, A. Aulabaugh,, W. Ding,, B. Kapoor,, L. Alksne,, K. Tabei,, and G. Ellestad. 2003. Kinetic mechanism of Staphylococcus aureus sortase SrtA. Biochemistry 42: 11307 11315.
29. Igarashi, T.,, E. Asaga,, and N. Goto. 2003. The sortase of Streptococcus mutans mediates cell wall anchoring of a surface protein antigen. Oral Microbiol. Immunol. 18: 266 269.
30. Ilangovan, U.,, H. Ton-That,, J. Iwahara,, O. Schneewind,, and R. T. Clubb. 2001. Structure of sortase, the transpeptidase that anchors proteins to the cell wall of Staphylococcus aureus. Proc. Nat. Acad. Sci. USA 98: 6056 6061.
31. Janulczyk, R.,, and M. Rasmussen. 2001. Improved pattern for genome-based screening identifies novel cell wall-attached proteins in gram-positive bacteria. Infect. Immun. 69: 4019 4026.
32. Jedrzejas, M. J. 2001. Pneumococcal virulence factors: structure and function. Microbiol. Mol. Biol. Rev. 65: 187 207.
33. Jonsson, I. M.,, S. K. Mazmanian,, O. Schneewind,, T. Bremell,, and A. Tarkowski. 2003. The role of Staphylococcus aureus sortase A and sortase B in murine arthritis. Microbes Infect. 5: 775 780.
34. Jonsson, I. M.,, S. K. Mazmanian,, O. Schneewind,, M. Verdrengh,, T. Bremell,, and A. Tarkowski. 2002. On the role of Staphylococcus aureus sortase and sortase-catalyzed surface protein anchoring in murine septic arthritis. J. Infect. Dis. 185: 1417 1424.
35. Kharat, A. S.,, and A. Tomasz. 2003. Inactivation of the srtA gene affects localization of surface proteins and decreases adhesion of Streptococcus pneumoniae to human pharyngeal cells in vitro. Infect. Immun. 71: 2758 2765.
36. Kim, S. H.,, D. S. Shin,, M. N. Oh,, S. C. Chung,, J. S. Lee,, I. M. Chang,, and K. B. Oh. 2003. Inhibition of sortase, a bacterial surface protein anchoring transpeptidase, by beta-sitosterol-3- O-glucopyranoside from Fritillaria verticillata. Biosci. Biotechnol. Biochem. 67: 2477 2479.
37. Kim, S. W.,, I. M. Chang,, and K. B. Oh. 2002. Inhibition of the bacterial surface protein anchoring transpeptidase sortase by medicinal plants. Biosci. Biotechnol. Biochem. 66: 2751 2754.
38. Kruger, R.,, S. Pesiridis,, and D. G. McCafferty,. 2001. Characterization of the Staphylococcus aureus sortase transpeptidase: a novel target for the development of chemotherapeutics against gram positive bacteria, p. 565 566. In M. Lebl, and R. Houghten (ed.), Peptides: The Wave of the Future. American Peptide Society, San Diego, Calif.
39. Kumar, S.,, and R. Nussinov. 1999. Salt bridge stability in monomeric proteins. J. Mol. Biol. 293: 1241 1255.
40. Lee, S. F.,, and T. L. Boran. 2003. Roles of sortase in surface expression of the major protein adhesin P1, saliva-induced aggregation and adherence, and cariogenicity of Streptococcus mutans. Infect. Immun. 71: 676 681.
41. Lewis, S. D.,, F. A. Johnson,, and J. A. Shafer. 1981. Effect of cysteine-25 on the ionization of histidine-159 in papain as determined by proton nuclear magnetic resonance spectroscopy. Evidence for a His-159-Cys-25 ion pair and its possible role in catalysis. Biochemistry 20: 48 51.
42. Li, T.,, M. K. Khah,, S. Slavnic,, I. Johansson,, and N. Stromberg. 2001. Different type 1 fimbrial genes and tropisms of commensal and potentially pathogenic Actinomyces spp. with different salivary acidic proline-rich protein and statherin ligand specificities. Infect. Immun. 69: 7224 7233.
43. Lofdahl, S.,, B. Guss,, M. Uhlen,, L. Philipson,, and M. Lindberg. 1983. Gene for staphylococcal protein A. Proc. Nat. Acad. Sci. USA 80: 697 701.
44. Lupas, A.,, H. Engelhardt,, J. Peters,, U. Santarius,, S. Volker,, and W. Baumeister. 1994. Domain structure of the Acetogenium kivui surface layer revealed by electron crystallography and sequence analysis. J. Bacteriol. 176: 1224 1233.
45. Marino, M.,, M. Banerjee,, R. Jonquieres,, P. Cossart,, and P. Ghosh. 2002. GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands. EMBO J. 21: 5623 5634.
46. Marino, M.,, L. Braun,, P. Cossart,, and P. Ghosh. 1999. Structure of the InlB leucine-rich repeats, a domain that triggers host cell invasion by the bacterial pathogen L. monocytogenes. Mol. Cell 4: 1063 1072.
47. Mazmanian, S. K.,, G. Liu,, T. T. Hung,, and O. Schneewind. 1999. Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285: 760 763.
48. Mazmanian, S. K.,, G. Liu,, E. R. Jensen,, E. Lenoy,, and O. Schneewind. 2000. Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections. Proc. Nat. Acad. Sci. USA 97: 5510 5515.
49. Mazmanian, S. K.,, H. Ton-That,, and O. Schneewind. 2001. Sortase-catalyzed anchoring of surface proteins to the cell wall of Staphylococcus aureus. Mol. Microbiol. 40: 1049 1057.
50. Mazmanian, S. K.,, H. Ton-That,, K. Su,, and O. Schneewind. 2002. An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc. Nat. Acad. Sci. USA 99: 2293 2298.
51. Navarre, W. W.,, and O. Schneewind. 1994. Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in gram-positive bacteria. Mol. Microbiol. 14: 115 121.
52. Navarre, W. W.,, and O. Schneewind. 1999. Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol. Mol. Biol. Rev. 63: 174 229.
53. Navarre, W. W.,, H. Ton-That,, K. F. Faull,, and O. Schneewind. 1998. Anchor structure of staphylococcal surface proteins. II. COOH-terminal structure of muramidase and amidase-solubilized surface protein. J. Biol. Chem. 273: 29135 29142.
54. Novick, R. P. 2000. Sortase: the surface protein anchoring transpeptidase and the LPXTG motif. Trends Microbiol. 8: 148 151.
55. Osaki, M.,, D. Takamatsu,, Y. Shimoji,, and T. Sekizaki. 2002. Characterization of Streptococcus suis genes encoding proteins homologous to sortase of gram-positive bacteria. J. Bacteriol. 184: 971 982.
56. Otto, H. H.,, and T. Schirmeister. 1997. Cysteine proteases and their inhibitors. Chem. Rev. 97: 133 171.
57. Pallen, M. J.,, A. C. Lam,, M. Antonio,, and K. Dunbar. 2001. An embarrassment of sortases: a richness of substrates? Trends Microbiol. 9: 97 101.
58. Palmer, J. T.,, D. Rasnick,, J. L. Klaus,, and D. Bromme. 1995. Vinyl sulfones as mechanism-based cysteine protease inhibitors. J. Med. Chem. 38: 3193 3196.
59. Pauly, T. A.,, T. Sulea,, M. Ammirati,, J. Sivaraman,, D. E. Danley,, M. C. Griffor,, A. V. Kamath,, I. K. Wang,, E. R. Laird,, A. P. Seddon,, R. Menard,, M. Cygler,, and V. L. Rath. 2003. Specificity determinants of human cathepsin S revealed by crystal structures of complexes. Biochemistry 42: 3203 3213.
60. Perry, A. M.,, H. Ton-That,, S. K. Mazmanian,, and O. Schneewind. 2002. Anchoring of surface proteins to the cell wall of Staphylococcus aureus. III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring. J. Biol. Chem. 277: 16241 16248.
61. Pinitglang, S.,, A. B. Watts,, M. Patel,, J. D. Reid,, M. A. Noble,, S. Gul,, A. Bokth,, A. Naeem,, H. Patel,, E. W. Thomas,, S. K. Sreedharan,, C. Verma,, and K. Brocklehurst. 1997. A classical enzyme active center motif lacks catalytic competence until modulated electrostatically. Biochemistry 36: 9968 9982.
62. Roche, F. M.,, R. Massey,, S. J. Peacock,, N. P. Day,, L. Visai,, P. Speziale,, A. Lam,, M. Pallen,, and T. J. Foster. 2003. Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences. Microbiology 149: 643 654.
63. Ruzin, A.,, A. Severin,, F. Ritacco,, K. Tabei,, G. Singh,, P. A. Bradford,, M. M. Siegel,, S. J. Projan,, and D. M. Shlaes. 2002. Further evidence that a cell wall precursor [C(55)-MurNAc-(peptide)-GlcNAc] serves as an acceptor in a sorting reaction. J. Bacteriol. 184: 2141 2147.
64. Sanchez-Puelles, J. M.,, J. M. Sanz,, J. L. Garcia,, and E. Garcia. 1990. Cloning and expression of gene fragments encoding the choline-binding domain of pneumococcal murein hydrolases. Gene 89: 69 75.
65. Sara, M. 2001. Conserved anchoring mechanisms between crystalline cell surface S-layer proteins and secondary cell wall polymers in Gram-positive bacteria? Trends Microbiology 9: 47 49.
66. Sarkany, Z.,, Z. Szeltner,, and L. Polgar. 2001. Thiolate-imidazolium ion pair is not an obligatory catalytic entity of cysteine peptidases: the active site of picornain 3C. Biochemistry 40: 10601 10606.
67. Schneewind, O.,, A. Fowler,, and K. F. Faull. 1995. Structure of the cell wall anchor of surface proteins in Staphylococcus aureus. Science 268: 103 106.
68. Schneewind, O.,, D. Mihaylova-Petkov,, and P. Model. 1993. Cell wall sorting signals in surface proteins of gram-positive bacteria. EMBO J. 12: 4803 4811.
69. Schneewind, O.,, P. Model,, and V. A. Fischetti. 1992. Sorting of protein-a to the staphylococcal cell wall. Cell 70: 267 281.
70. Schneewind, O.,, V. Pancholi,, and V. A. Fischetti,. 1991. Surface proteins from gram-positive cocci have a common motif for membrane anchoring, p. 152 154. In G. M. Dunny,, P. P. Cleary,, and L. L. McKay (ed.), Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci. American Society for Microbiology, Washington, D.C.
71. Scott, C. J.,, A. McDowell,, S. L. Martin,, J. F. Lynas,, K. Vandenbroeck,, and B. Walker. 2002. Irreversible inhibition of the bacterial cysteine protease-transpeptidase sortase (SrtA) by substrate-derived affinity labels. Biochem. J. 366: 953 958.
72. Severin, A.,, A. Figueiredo,, and A. Tomasz. 1996. Separation of abnormal cell wall composition from penicillin resistance through genetic transformation of Streptococcus pneumoniae. J. Bacteriol. 178: 1788 1792.
73. Sjoquist, J.,, B. Meloun,, and H. Hjelm. 1972a. Protein A isolated from Staphylococcus aureus after digestion with lysostaphin. Eur. J. Biochem. 29: 572 578.
74. Sjoquist, J.,, J. Movitz,, I. B. Johansson,, and H. Hjelm. 1972b. Localization of protein A in the bacteria. Eur. J. Biochem. 30: 190 194.
75. Somoza, J. R.,, J. T. Palmer,, and J. D. Ho. 2002. The crystal structure of human cathepsin F and its implications for the development of novel immunomodulators. J. Mol. Biol. 322: 559 568.
76. Somoza, J. R.,, H. Zhan,, K. K. Bowman,, L. Yu,, K. D. Mortara,, J. T. Palmer,, J. M. Clark,, and M. E. McGrath. 2000. Crystal structure of human cathepsin V. Biochemistry 39: 12543 12551.
77. Storer, A. C.,, and R. Menard. 1994. Catalytic mechanism in papain family of cysteine peptidases. Methods Enzymol. 244: 486 500.
78. Strominger, J. L. 1965. Biochemistry of the cell wall of Staphylococcus aureus. Ann. N.Y. Acad. Sci. 128: 59 61.
79. Strominger, J. L.,, K. Izaki,, M. Matsuhashi,, and D. J. Tipper. 1967. Peptidoglycan transpeptidase and D-alanine carboxypeptidase: penicillin-sensitive enzymatic reactions. Fed. Proc. 26: 9 22.
80. Strominger, J. L.,, and D. J. Tipper. 1965. Bacterial cell wall synthesis and structure in relation to the mechanism of action of penicillins and other antibacterial agents. Am. J. Med. 39: 708 721.
81. Tipper, D. J.,, and J. L. Strominger. 1965. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc. Nat. Acad. Sci. USA 54: 1133 1141.
82. Ton-That, H.,, K. F. Faull,, and O. Schneewind. 1997. Anchor structure of staphylococcal surface proteins—a branched peptide that links the carboxyl terminus of proteins to the cell wall. J. Biol. Chem. 272: 22285 22292.
83. Ton-That, H.,, H. Labischinski,, B. Berger-Bachi,, and O. Schneewind. 1998. Anchor structure of staphylococcal surface proteins. III. Role of the FemA, FemB, and FemX factors in anchoring surface proteins to the bacterial cell wall. J. Biol. Chem. 273: 29143 29149.
84. Ton-That, H.,, G. Liu,, S. K. Mazmanian,, K. F. Faull,, and O. Schneewind. 1999. Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif. Proc. Nat. Acad. Sci. USA 96: 12424 12429.
85. Ton-That, H.,, S. K. Mazmanian,, L. Alksne,, and O. Schneewind. 2002. Anchoring of surface proteins to the cell wall of Staphylococcus aureus—cysteine 184 and histidine 120 of sortase form a thiolate-imidazolium ion pair for catalysis. J. Biol. Chem. 277: 7447 7452.
86. Ton-That, H.,, S. K. Mazmanian,, K. F. Faull,, and O. Schneewind. 2000. Anchoring of surface proteins to the cell wall of Staphylococcus aureus—sortase catalyzed in vitro transpeptidation reaction using LPXTG peptide and NH2-Gly(3) substrates. J. Biol. Chem. 275: 9876 9881.
87. Ton-That, H.,, and O. Schneewind. 1999. Anchor structure of staphylococcal surface proteins IV. Inhibitors of the cell wall sorting reaction. J. Biol. Chem. 274: 24316 24320.
88. Uhlen, M.,, B. Guss,, B. Nilsson,, S. Gatenbeck,, L. Philipson,, and M. Lindberg. 1984. Complete sequence of the staphylococcal gene encoding protein A. J. Biol. Chem. 259: 1695 1702.
89. Varea, J.,, J. L. Saiz,, C. Lopez-Zumel,, B. Monterroso,, F. J. Medrano,, J. L. Arrondo,, I. Iloro,, J. Laynez,, J. L. Garcia,, and M. Menendez. 2000. Do sequence repeats play an equivalent role in the choline-binding module of pneumococcal LytA amidase? J. Biol. Chem. 275: 26842 26855.
90. Whittaker, C. J.,, D. L. Clemans,, and P. E. Kolenbrander. 1996. Insertional inactivation of an intrageneric coaggregation- relevant adhesion locus from Streptococcus gordonii DL1 (challis). Infect. Immun. 64: 4137 4142.
91. Xu, Q.,, W. Gao,, S.-Y. Ding,, R. Kenig,, Y. Shoham,, E. A. Bayer,, and R. Lamed. 2003. The cellulosome system of Acetivibrio cellulolyticus includes a novel type of adaptor protein and a cell surface anchoring protein. J. Bacteriol. 185: 4548 4557.

Tables

Generic image for table
Untitled

Citation: Connolly K, Clubb R. 2005. Sortase Pathways in Gram-Positive Bacteria, p 101-128. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch7

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error