4r5l - Revision history

OCA at 12:50, 1 March 2024

OCA — Fri, 01 Mar 2024 12:50:28 GMT

←Older revision		Revision as of 12:50, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<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>		<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>
-	</td></tr><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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.9701Å</td></tr>
		+	<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>
	<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>		<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 ==
	[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]		[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]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	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.
-
-	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>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4r5l" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]		*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:41, 2 March 2023

OCA — Thu, 02 Mar 2023 06:41:15 GMT

←Older revision		Revision as of 06:41, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='4r5l' size='340' side='right'caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>		<StructureSection load='4r5l' size='340' side='right'caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<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>	+	<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>
-	</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>~~	+	</td></tr><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>
-	<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>	+	<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>
-	<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>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[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]	+	[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]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[Heat Shock ~~Proteins~~\|Heat Shock ~~Proteins~~]]	+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Ecoli~~]]	+	[[Category: Escherichia coli K-12]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: George~~, D L~~]]	+	[[Category: George DL]]
-	[[Category: Leu~~, J I~~]]	+	[[Category: Leu JI]]
-	[[Category: Marmorstein, R]]	+	[[Category: Marmorstein R]]
-	[[Category: Murphy~~, M E~~]]	+	[[Category: Murphy ME]]
-	[[Category: Zhang, P]]	+	[[Category: Zhang P]]
-	~~[[Category: Beta sheet]]~~	+
-	~~[[Category: Chaperone]]~~	+
-	~~[[Category: Helical bundle]]~~	+
-	~~[[Category: Membrane~~]]	+

OCA at 10:08, 1 May 2019

OCA — Wed, 01 May 2019 10:08:14 GMT

←Older revision		Revision as of 10:08, 1 May 2019
Line 1:		Line 1:

	==Crystal structure of the DnaK C-terminus (Dnak-SBD-C)==		==Crystal structure of the DnaK C-terminus (Dnak-SBD-C)==
-	<StructureSection load='4r5l' size='340' side='right' caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>	+	<StructureSection load='4r5l' size='340' side='right'caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>	+	<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>
	</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>		</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>
		+	<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>
	<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>		<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>
	</table>		</table>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Ecoli]]
		+	[[Category: Large Structures]]
	[[Category: George, D L]]		[[Category: George, D L]]
	[[Category: Leu, J I]]		[[Category: Leu, J I]]

OCA at 11:27, 4 August 2016

OCA — Thu, 04 Aug 2016 11:27:18 GMT

←Older revision		Revision as of 11:27, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the DnaK C-terminus (Dnak-SBD-C)==		==Crystal structure of the DnaK C-terminus (Dnak-SBD-C)==
	<StructureSection load='4r5l' size='340' side='right' caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>		<StructureSection load='4r5l' size='340' side='right' caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>		<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>
	</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>		</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>
-	<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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>	+	<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>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4r5l" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Proteins\|Heat Shock Proteins]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:53, 24 December 2014

OCA — Wed, 24 Dec 2014 13:53:08 GMT

←Older revision		Revision as of 13:53, 24 December 2014
Line 6:		Line 6:
	<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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>		<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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[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]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:54, 3 December 2014

OCA — Wed, 03 Dec 2014 07:54:22 GMT

←Older revision		Revision as of 07:54, 3 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>		<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>
-	</td></tr><tr><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><br>	+	</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>
-	<tr><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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>	+	<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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 18:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: George, D L.]]	+	[[Category: George, D L]]
-	[[Category: Leu, J I.]]	+	[[Category: Leu, J I]]
-	[[Category: Marmorstein, R.]]	+	[[Category: Marmorstein, R]]
-	[[Category: Murphy, M E.]]	+	[[Category: Murphy, M E]]
-	[[Category: Zhang, P.]]	+	[[Category: Zhang, P]]
	[[Category: Beta sheet]]		[[Category: Beta sheet]]
	[[Category: Chaperone]]		[[Category: Chaperone]]
	[[Category: Helical bundle]]		[[Category: Helical bundle]]
	[[Category: Membrane]]		[[Category: Membrane]]

OCA at 10:03, 10 September 2014

OCA — Wed, 10 Sep 2014 10:03:08 GMT

←Older revision		Revision as of 10:03, 10 September 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of the DnaK C-terminus (Dnak-SBD-C)==
		+	<StructureSection load='4r5l' size='340' side='right' caption='[[4r5l]], [[Resolution\|resolution]] 2.97Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4r5l]] is a 4 chain structure. 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>
		+	</td></tr><tr><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><br>
		+	<tr><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://www.rcsb.org/pdb/explore.do?structureId=4r5l RCSB], [http://www.ebi.ac.uk/pdbsum/4r5l PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	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.

-	~~The entry 4r5l is ON HOLD~~	+	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>

-	~~Authors~~: Leu, J.I., ~~Zhang, P~~., Murphy, M.E., ~~Marmorstein, R., George, D.L~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of the DnaK C-terminus (Dnak-SBD-C)~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: George, D L.]]
		+	[[Category: Leu, J I.]]
		+	[[Category: Marmorstein, R.]]
		+	[[Category: Murphy, M E.]]
		+	[[Category: Zhang, P.]]
		+	[[Category: Beta sheet]]
		+	[[Category: Chaperone]]
		+	[[Category: Helical bundle]]
		+	[[Category: Membrane]]

OCA: Protected "4r5l" [edit=sysop:move=sysop]

OCA — Wed, 27 Aug 2014 07:02:44 GMT

Protected "4r5l" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:02, 27 August 2014

OCA: New page: '''Unreleased structure''' The entry 4r5l is ON HOLD Authors: Leu, J.I., Zhang, P., Murphy, M.E., Marmorstein, R., George, D.L. Description: Crystal structure of the DnaK C-terminus (D...

OCA — Wed, 27 Aug 2014 07:02:43 GMT

New page: '''Unreleased structure''' The entry 4r5l is ON HOLD Authors: Leu, J.I., Zhang, P., Murphy, M.E., Marmorstein, R., George, D.L. Description: Crystal structure of the DnaK C-terminus (D...

New page

'''Unreleased structure'''

The entry 4r5l is ON HOLD

Authors: Leu, J.I., Zhang, P., Murphy, M.E., Marmorstein, R., George, D.L.

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