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| | <StructureSection load='6u33' size='340' side='right'caption='[[6u33]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='6u33' size='340' side='right'caption='[[6u33]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6u33]] is a 1 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=6U33 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U33 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u33]] is a 1 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=6U33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U33 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 1.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6u2s|6u2s]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lukNF, lukD, BTN44_02870, EP54_14125, EQ90_10595, ER624_13605, HMPREF3211_01500, NCTC10654_01892, NCTC13131_06007, RK64_09800 ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6u33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u33 OCA], [https://pdbe.org/6u33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u33 RCSB], [https://www.ebi.ac.uk/pdbsum/6u33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u33 ProSAT]</span></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=6u33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u33 OCA], [http://pdbe.org/6u33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u33 RCSB], [http://www.ebi.ac.uk/pdbsum/6u33 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u33 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LUKDV_STAA8 LUKDV_STAA8] Part of a bi-component leucotoxin that acts by forming pores in the membrane of the target cells. The activity of LukEv-LukDv to rabbit leukocytes is similar to that of the Panton-Valentine leucocidin (PVL). LukEv-LukDv is hemolytic to rabbit red blood cells although the activity is only 8% of gamma-hemolysin.<ref>PMID:12636257</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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
LUKDV_STAA8 Part of a bi-component leucotoxin that acts by forming pores in the membrane of the target cells. The activity of LukEv-LukDv to rabbit leukocytes is similar to that of the Panton-Valentine leucocidin (PVL). LukEv-LukDv is hemolytic to rabbit red blood cells although the activity is only 8% of gamma-hemolysin.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morinaga N, Kaihou Y, Noda M. Purification, cloning and characterization of variant LukE-LukD with strong leukocidal activity of staphylococcal bi-component leukotoxin family. Microbiol Immunol. 2003;47(1):81-90. PMID:12636257
- ↑ 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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