4yg4: Difference between revisions
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==HipB-O1-O1* complex== | ==HipB-O1-O1* complex== | ||
<StructureSection load='4yg4' size='340' side='right' caption='[[4yg4]], [[Resolution|resolution]] 3.50Å' scene=''> | <StructureSection load='4yg4' size='340' side='right'caption='[[4yg4]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4yg4]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YG4 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4yg4]] 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=4YG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YG4 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yg4 OCA], [https://pdbe.org/4yg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yg4 RCSB], [https://www.ebi.ac.uk/pdbsum/4yg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yg4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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;"> | |||
== 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<ref>PMID:26222023</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4yg4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Escherichia coli K-12]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Schumacher MA]] | ||
