View source for 3tpe


==The phipa p3121 structure==
<StructureSection load='3tpe' size='340' side='right'caption='[[3tpe]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tpe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TPE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=3tpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tpe OCA], [https://pdbe.org/3tpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tpe RCSB], [https://www.ebi.ac.uk/pdbsum/3tpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tpe ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HipA is a bacterial serine/threonine protein kinase that phosphorylates targets, bringing about persistence and multidrug tolerance. Autophosphorylation of residue Ser150 is a critical regulatory mechanism of HipA function. Intriguingly, Ser150 is not located on the activation loop, as are other kinases; instead, it is in the protein core, where it forms part of the ATP-binding "P loop motif." How this buried residue is phosphorylated and regulates kinase activity is unclear. Here, we report multiple structures that reveal the P loop motif's exhibition of a remarkable "in-out" conformational equilibrium, which allows access to Ser150 and its intermolecular autophosphorylation. Phosphorylated Ser150 stabilizes the "out state," which inactivates the kinase by disrupting the ATP-binding pocket. Thus, our data reveal a mechanism of protein kinase regulation that is vital for multidrug tolerance and persistence, as kinase inactivation provides the critical first step in allowing dormant cells to revert to the growth phenotype and to reinfect the host.

Role of Unusual P Loop Ejection and Autophosphorylation in HipA-Mediated Persistence and Multidrug Tolerance.,Schumacher MA, Min J, Link TM, Guan Z, Xu W, Ahn YH, Soderblom EJ, Kurie JM, Evdokimov A, Moseley MA, Lewis K, Brennan RG Cell Rep. 2012 Sep 27;2(3):518-25. doi: 10.1016/j.celrep.2012.08.013. Epub 2012, Sep 20. PMID:22999936<ref>PMID:22999936</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3tpe" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Brennan RG]]
[[Category: Link T]]
[[Category: Schumacher MA]]