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| | ==HipB-O1-O2 complex/P21212 crystal form== | | ==HipB-O1-O2 complex/P21212 crystal form== |
| - | <StructureSection load='4yg1' size='340' side='right' caption='[[4yg1]], [[Resolution|resolution]] 3.25Å' scene=''> | + | <StructureSection load='4yg1' size='340' side='right'caption='[[4yg1]], [[Resolution|resolution]] 3.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yg1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YG1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yg1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YG1 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yg4|4yg4]], [[4yg7|4yg7]]</td></tr> | + | </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=4yg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yg1 OCA], [https://pdbe.org/4yg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yg1 RCSB], [https://www.ebi.ac.uk/pdbsum/4yg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yg1 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hipB, b1508, JW1501 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
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| - | <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=4yg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yg1 OCA], [http://pdbe.org/4yg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yg1 RCSB], [http://www.ebi.ac.uk/pdbsum/4yg1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yg1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HIPB_ECOLI HIPB_ECOLI]] Antitoxin component of a toxin-antitoxin (TA) module. Neutralizes the toxic effect of cognate toxin HipA. Binds to operator sites with the consensus sequence 5-'TATCCN(8)GGATA-3' to repress the hipBA operon promoter. | + | [https://www.uniprot.org/uniprot/HIPB_ECOLI HIPB_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Neutralizes the toxic effect of cognate toxin HipA. Binds to operator sites with the consensus sequence 5-'TATCCN(8)GGATA-3' to repress the hipBA operon promoter. |
| | <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 4yg1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4yg1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Schumacher, M A]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Hipa]] | + | [[Category: Large Structures]] |
| - | [[Category: Multidrug tolerance]] | + | [[Category: Schumacher MA]] |
| - | [[Category: Persistence]]
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| - | [[Category: Transcription-dna complex]]
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| Structural highlights
Function
HIPB_ECOLI Antitoxin component of a toxin-antitoxin (TA) module. Neutralizes the toxic effect of cognate toxin HipA. Binds to operator sites with the consensus sequence 5-'TATCCN(8)GGATA-3' to repress the hipBA operon promoter.
Publication Abstract from PubMed
Multidrug tolerance is largely responsible for chronic infections and caused by a small population of dormant cells called persisters. Selection for survival in the presence of antibiotics produced the first genetic link to multidrug tolerance: a mutant in the Escherichia coli hipA locus. HipA encodes a serine-protein kinase, the multidrug tolerance activity of which is neutralized by binding to the transcriptional regulator HipB and hipBA promoter. The physiological role of HipA in multidrug tolerance, however, has been unclear. Here we show that wild-type HipA contributes to persister formation and that high-persister hipA mutants cause multidrug tolerance in urinary tract infections. Perplexingly, high-persister mutations map to the N-subdomain-1 of HipA far from its active site. Structures of higher-order HipA-HipB-promoter complexes reveal HipA forms dimers in these assemblies via N-subdomain-1 interactions that occlude their active sites. High-persistence mutations, therefore, diminish HipA-HipA dimerization, thereby unleashing HipA to effect multidrug tolerance. Thus, our studies reveal the mechanistic basis of heritable, clinically relevant antibiotic tolerance.
HipBA-promoter structures reveal the basis of heritable multidrug tolerance.,Schumacher MA, Balani P, Min J, Chinnam NB, Hansen S, Vulic M, Lewis K, Brennan RG Nature. 2015 Aug 6;524(7563):59-64. doi: 10.1038/nature14662. Epub 2015 Jul 29. PMID:26222023[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schumacher MA, Balani P, Min J, Chinnam NB, Hansen S, Vulic M, Lewis K, Brennan RG. HipBA-promoter structures reveal the basis of heritable multidrug tolerance. Nature. 2015 Aug 6;524(7563):59-64. doi: 10.1038/nature14662. Epub 2015 Jul 29. PMID:26222023 doi:http://dx.doi.org/10.1038/nature14662
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