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| | <StructureSection load='6u3t' size='340' side='right'caption='[[6u3t]], [[Resolution|resolution]] 2.79Å' scene=''> | | <StructureSection load='6u3t' size='340' side='right'caption='[[6u3t]], [[Resolution|resolution]] 2.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6u3t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U3T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U3T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u3t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U3T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PQJ:fos-choline-14'>PQJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.79Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hly, hla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PQJ:fos-choline-14'>PQJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6u3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u3t OCA], [http://pdbe.org/6u3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u3t RCSB], [http://www.ebi.ac.uk/pdbsum/6u3t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u3t ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6u3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u3t OCA], [https://pdbe.org/6u3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u3t RCSB], [https://www.ebi.ac.uk/pdbsum/6u3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u3t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HLA_STAAU HLA_STAAU]] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity. | + | [https://www.uniprot.org/uniprot/HLA_STAAU HLA_STAAU] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6u3t" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6u3t" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Hemolysin 3D structures|Hemolysin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kozhaya, L]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Liu, J]] | + | [[Category: Kozhaya L]] |
| - | [[Category: Lu, M]] | + | [[Category: Liu J]] |
| - | [[Category: Torres, V J]] | + | [[Category: Lu M]] |
| - | [[Category: Unutmaz, D]] | + | [[Category: Torres VJ]] |
| - | [[Category: Alpha-toxin]]
| + | [[Category: Unutmaz D]] |
| - | [[Category: Leukocidin]]
| + | |
| - | [[Category: Mrsa]]
| + | |
| - | [[Category: Pvl]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
HLA_STAAU Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity.
Publication Abstract from PubMed
The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton-Valentine leukocidin (PVL) and alpha-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and alpha-toxin in their soluble, monomeric and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and alpha-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.
Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence.,Liu J, Kozhaya L, Torres VJ, Unutmaz D, Lu M J Biol Chem. 2020 Mar 16. pii: RA120.012697. doi: 10.1074/jbc.RA120.012697. PMID:32179646[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu J, Kozhaya L, Torres VJ, Unutmaz D, Lu M. Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence. J Biol Chem. 2020 Mar 16. pii: RA120.012697. doi: 10.1074/jbc.RA120.012697. PMID:32179646 doi:http://dx.doi.org/10.1074/jbc.RA120.012697
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