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| | <StructureSection load='4yg7' size='340' side='right'caption='[[4yg7]], [[Resolution|resolution]] 3.77Å' scene=''> | | <StructureSection load='4yg7' size='340' side='right'caption='[[4yg7]], [[Resolution|resolution]] 3.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yg7]] is a 8 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=4YG7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YG7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yg7]] is a 8 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=4YG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YG7 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yg1|4yg1]], [[4yg4|4yg4]]</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]] 3.77Å</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]), hipA, b1507, JW1500 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=4yg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yg7 OCA], [https://pdbe.org/4yg7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yg7 RCSB], [https://www.ebi.ac.uk/pdbsum/4yg7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yg7 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=4yg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yg7 OCA], [http://pdbe.org/4yg7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yg7 RCSB], [http://www.ebi.ac.uk/pdbsum/4yg7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yg7 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. [[http://www.uniprot.org/uniprot/HIPA_ECOLI HIPA_ECOLI]] Toxic component of a toxin-antitoxin (TA) module. Autophosphorylates (Ser-150) and phosphorylates EF-Tu in vitro (on 'Thr-383'), may act on other proteins as well. The hipA7 mutation leads to increased generation of persister cells, cells that survive antibiotic treatment probably by entering into a dormant state. Wild-type cells produce persisters at a frequency of 10-6 to 10-5 whereas mutant hipA7 cells produce persisters at a frequency of 10-2. Generation of persister cells requires (p)ppGpp as cells lacking relA or relA/spoT generate fewer or no persister cells respectively compared to hipA7. Low level expression of HipA causes cell filamentation and depending on the protein level is toxic enough to reduce cell growth or even kill cells. Expression of wild-type HipA also leads to high antibiotic tolerance of the survivor cells. The toxic effect of HipA is neutralized by its cognate antitoxin HipB. With HipB acts as a corepressor for transcription of the hipBA promoter.<ref>PMID:17041039</ref> <ref>PMID:6348026</ref> <ref>PMID:8021189</ref> <ref>PMID:14622409</ref> <ref>PMID:19150849</ref> | + | [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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| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[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: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Schumacher MA]] |
| - | [[Category: Schumacher, M A]] | + | |
| - | [[Category: Autorepression]]
| + | |
| - | [[Category: Multidrug tolerance]]
| + | |
| - | [[Category: Persistence]]
| + | |
| - | [[Category: Promoter]]
| + | |
| - | [[Category: Transcription]]
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| - | [[Category: Transferase-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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