4r5l

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<StructureSection load='4r5l' size='340' side='right'caption='[[4r5l]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
<StructureSection load='4r5l' size='340' side='right'caption='[[4r5l]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4r5l]] is a 4 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=4R5L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R5L FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure with sequence from [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=4R5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5L FirstGlance]. <br>
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</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9701&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dnaK, groP, grpF, seg, b0014, JW0013 ([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='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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4r5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5l OCA], [http://pdbe.org/4r5l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5l ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5l OCA], [https://pdbe.org/4r5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [https://www.ebi.ac.uk/pdbsum/4r5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5l ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/DNAK_ECOLI DNAK_ECOLI]] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332]
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[https://www.uniprot.org/uniprot/DNAK_ECOLI DNAK_ECOLI] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The stress-inducible mammalian heat shock protein 70 (HSP70) and its bacterial orthologue DnaK are highly conserved nucleotide binding molecular chaperones. They represent critical regulators of cellular proteostasis, especially during conditions of enhanced stress. Cancer cells rely on HSP70 for survival, and this chaperone represents an attractive new therapeutic target. We have used a structure-activity approach and biophysical methods to characterize a class of inhibitors that bind to a unique allosteric site within the C-terminus of HSP70 and DnaK. Data from X-ray crystallography together with isothermal titration calorimetry, mutagenesis, and cell-based assays indicate that these inhibitors bind to a previously unappreciated allosteric pocket formed within the non-ATP-bound protein state. Moreover, binding of inhibitor alters the local protein conformation, resulting in reduced chaperone-client interactions and impairment of proteostasis. Our findings thereby provide a new chemical scaffold and target platform for both HSP70 and DnaK; these will be important tools with which to interrogate chaperone function and to aid ongoing efforts to optimize potency and efficacy in developing modulators of these chaperones for therapeutic use.
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Structural Basis for the Inhibition of HSP70 and DnaK Chaperones by Small-Molecule Targeting of a C-Terminal Allosteric Pocket.,Leu JI, Zhang P, Murphy ME, Marmorstein R, George DL ACS Chem Biol. 2014 Aug 28. PMID:25148104<ref>PMID:25148104</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4r5l" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Heat Shock Proteins|Heat Shock Proteins]]
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*[[Heat Shock Protein structures|Heat Shock Protein structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Ecoli]]
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[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: George, D L]]
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[[Category: George DL]]
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[[Category: Leu, J I]]
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[[Category: Leu JI]]
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[[Category: Marmorstein, R]]
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[[Category: Marmorstein R]]
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[[Category: Murphy, M E]]
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[[Category: Murphy ME]]
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[[Category: Zhang, P]]
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[[Category: Zhang P]]
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[[Category: Beta sheet]]
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[[Category: Chaperone]]
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[[Category: Helical bundle]]
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[[Category: Membrane]]
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Current revision

Crystal structure of the DnaK C-terminus (Dnak-SBD-C)

PDB ID 4r5l

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