Enzymes
| UniProtKB help_outline | 1 proteins |
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Name help_outline
4-O-({poly[1-D-ribitylphospho]}-di{[2R]-glycerylphospho})-N-acetyl-β-D-mannosaminyl-(1→4)-N-acetyl-α-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphate
Identifier
CHEBI:133896
Charge
-5
Formula
(C5H10O7P)n.C77H128N2O27P4
Search links
Involved in 4 reaction(s)
Find proteins in UniProtKB for this molecule
Form(s) in this reaction:
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Identifier: RHEA-COMP:12840Polymer name: 4-O-[(D-ribitylphospho)(n)-di{(2R)-glycerylphospho}]-N-acetyl-β-D-mannosaminyl-(1→4)-N-acetyl-α-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphatePolymerization index help_outline nFormula C77H128N2O27P4(C5H10O7P)nCharge (-4)(-1)nMol File for the polymer
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- Name help_outline UDP-N-acetyl-α-D-glucosamine Identifier CHEBI:57705 (Beilstein: 4286654) help_outline Charge -2 Formula C17H25N3O17P2 InChIKeyhelp_outline LFTYTUAZOPRMMI-CFRASDGPSA-L SMILEShelp_outline CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1ccc(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 88 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Name help_outline
4-O-([3-N-acetyl-β-D-glucosaminyl-1-D-ribitylphospho]n-di{[2R]-1-glycerylphospho})-N-acetyl-β-D-mannosaminyl-(1→4)-N-acetyl-α-D-glucosaminyl ditrans,octacis-undecaprenyl diphosphate
Identifier
CHEBI:142885
Charge
-5
Formula
(C13H23NO12P)n.C77H128N2O27P4
Search links
Involved in 1 reaction(s)
Find proteins in UniProtKB for this molecule
Form(s) in this reaction:
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Identifier: RHEA-COMP:15259Polymer name: 4-O-([3-N-acetyl-β-D-glucosaminyl-1-D-ribitylphospho](n)-di{[2R]-1-glycerylphospho})-N-acetyl-β-D-mannosaminyl-(1→4)-N-acetyl-α-D-glucosaminyl di-trans,octa-cis-undecaprenyl diphosphatePolymerization index help_outline nFormula C77H128N2O27P4(C13H23NO12P)nCharge (-4)(-1)nMol File for the polymer
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- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline UDP Identifier CHEBI:58223 Charge -3 Formula C9H11N2O12P2 InChIKeyhelp_outline XCCTYIAWTASOJW-XVFCMESISA-K SMILEShelp_outline O[C@@H]1[C@@H](COP([O-])(=O)OP([O-])([O-])=O)O[C@H]([C@@H]1O)n1ccc(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 576 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:58948 | RHEA:58949 | RHEA:58950 | RHEA:58951 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity.
Gerlach D., Guo Y., De Castro C., Kim S.H., Schlatterer K., Xu F.F., Pereira C., Seeberger P.H., Ali S., Codee J., Sirisarn W., Schulte B., Wolz C., Larsen J., Molinaro A., Lee B.L., Xia G., Stehle T., Peschel A.
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans<sup>1,2</sup>. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients<sup>3</sup>. Previous va ... >> More
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans<sup>1,2</sup>. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients<sup>3</sup>. Previous vaccine development programs have not been successful<sup>4</sup>. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)<sup>5,6</sup>. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS<sup>7</sup>, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5-40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences. << Less