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| | ==Molecular Basis of Vancomycin Resistance Transfer in Staphylococcus aureus== | | ==Molecular Basis of Vancomycin Resistance Transfer in Staphylococcus aureus== |
| - | <StructureSection load='4ht4' size='340' side='right' caption='[[4ht4]], [[Resolution|resolution]] 2.91Å' scene=''> | + | <StructureSection load='4ht4' size='340' side='right'caption='[[4ht4]], [[Resolution|resolution]] 2.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ht4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HT4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HT4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ht4]] 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=4HT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HT4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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]] 2.907Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <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">nes, NES from pLW1043 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</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=4ht4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht4 OCA], [https://pdbe.org/4ht4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ht4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ht4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ht4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ht4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ht4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ht4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q53632_STAAU Q53632_STAAU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ht4" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Staphylococcus aureus]] | | [[Category: Staphylococcus aureus]] |
| - | [[Category: Edwards, J S]] | + | [[Category: Edwards JS]] |
| - | [[Category: Conjugative transfer]]
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| - | [[Category: Dna hairpin]]
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| - | [[Category: Dna relaxase]]
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| - | [[Category: Hydrolase-dna complex]]
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| - | [[Category: S. aureus]]
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| - | [[Category: Vancomycin resistance plasmid]]
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| Structural highlights
Function
Q53632_STAAU
Publication Abstract from PubMed
Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase-DNA complex crystal structure reveals unique protein-DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES-DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.
Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.,Edwards JS, Betts L, Frazier ML, Pollet RM, Kwong SM, Walton WG, Ballentine WK 3rd, Huang JJ, Habibi S, Del Campo M, Meier JL, Dervan PB, Firth N, Redinbo MR Proc Natl Acad Sci U S A. 2013 Jan 28. PMID:23359708[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Edwards JS, Betts L, Frazier ML, Pollet RM, Kwong SM, Walton WG, Ballentine WK 3rd, Huang JJ, Habibi S, Del Campo M, Meier JL, Dervan PB, Firth N, Redinbo MR. Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus. Proc Natl Acad Sci U S A. 2013 Jan 28. PMID:23359708 doi:http://dx.doi.org/10.1073/pnas.1219701110
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