5exw - Revision history

OCA at 08:32, 12 July 2023

OCA — Wed, 12 Jul 2023 08:32:32 GMT

←Older revision		Revision as of 08:32, 12 July 2023
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	<StructureSection load='5exw' size='340' side='right'caption='[[5exw]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='5exw' size='340' side='right'caption='[[5exw]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5exw]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5EXW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5exw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EXW FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=7DT:7~~-~~DEAZAADENOSINE-5-TRIPHOSPHATE'>7DT</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]] 1.9Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5evz\|5evz]], [[5ex5\|5ex5]], [[5ey4\|5ey4]], [[5f0x\|5f0x]], [[5f1x\|5f1x]], [[5f2r\|5f2r]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7DT:7-DEAZAADENOSINE-5-TRIPHOSPHATE'>7DT</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><~~b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">HSPA5, GRP78 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=5exw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exw OCA], [https://pdbe.org/5exw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5exw RCSB], [https://www.ebi.ac.uk/pdbsum/5exw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5exw ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5exw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exw OCA], [~~http~~://pdbe.org/5exw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5exw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5exw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5exw ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/~~GRP78_HUMAN GRP78_HUMAN~~]~~] Note=~~Autoantigen in rheumatoid arthritis.<ref>PMID:11160188</ref>	+	[https://www.uniprot.org/uniprot/BIP_HUMAN BIP_HUMAN] Autoantigen in rheumatoid arthritis.<ref>PMID:11160188</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~GRP78_HUMAN GRP78_HUMAN~~]~~] Probably~~ plays a role in ~~facilitating~~ the ~~assembly~~ of ~~multimeric~~ protein ~~complexes inside~~ the ER.<ref>PMID:2294010</ref>	+	[https://www.uniprot.org/uniprot/BIP_HUMAN BIP_HUMAN] Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:G3I8R9][UniProtKB:P20029]<ref>PMID:1550958</ref> <ref>PMID:19538957</ref> <ref>PMID:2294010</ref> <ref>PMID:23769672</ref> <ref>PMID:23990668</ref> <ref>PMID:28332555</ref> <ref>PMID:29719251</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5exw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5exw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Antoshchenko, T]]	+	[[Category: Antoshchenko T]]
-	[[Category: Hughes~~, S J~~]]	+	[[Category: Hughes SJ]]
-	[[Category: Park~~, H W~~]]	+	[[Category: Park HW]]
-	[[Category: Pizarro, J]]	+	[[Category: Pizarro J]]
-	[[Category: Song~~, J H]]~~	+	[[Category: Song JH]]
-	~~[[Category: Atpase domain]]~~	+
-	~~[[Category: Chaperone]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Nucleotide-binding~~]]	+

OCA at 07:49, 29 April 2020

OCA — Wed, 29 Apr 2020 07:49:56 GMT

←Older revision		Revision as of 07:49, 29 April 2020
Line 1:		Line 1:

	==Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP==		==Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP==
-	<StructureSection load='5exw' size='340' side='right' caption='[[5exw]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='5exw' size='340' side='right'caption='[[5exw]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5exw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXW OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5EXW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5exw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EXW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7DT:7-DEAZAADENOSINE-5-TRIPHOSPHATE'>7DT</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7DT:7-DEAZAADENOSINE-5-TRIPHOSPHATE'>7DT</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5evz\|5evz]], [[5ex5\|5ex5]], [[5ey4\|5ey4]], [[5f0x\|5f0x]], [[5f1x\|5f1x]], [[5f2r\|5f2r]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5evz\|5evz]], [[5ex5\|5ex5]], [[5ey4\|5ey4]], [[5f0x\|5f0x]], [[5f1x\|5f1x]], [[5f2r\|5f2r]]</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=5exw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exw OCA], [http://pdbe.org/5exw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exw RCSB], [http://www.ebi.ac.uk/pdbsum/5exw PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSPA5, GRP78 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5exw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exw OCA], [http://pdbe.org/5exw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exw RCSB], [http://www.ebi.ac.uk/pdbsum/5exw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5exw ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Antoshchenko, T]]		[[Category: Antoshchenko, T]]
	[[Category: Hughes, S J]]		[[Category: Hughes, S J]]

OCA at 15:13, 20 June 2016

OCA — Mon, 20 Jun 2016 15:13:13 GMT

←Older revision		Revision as of 15:13, 20 June 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5exw is ~~ON HOLD~~	+	==Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP==
		+	<StructureSection load='5exw' size='340' side='right' caption='[[5exw]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5exw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7DT:7-DEAZAADENOSINE-5-TRIPHOSPHATE'>7DT</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5evz\|5evz]], [[5ex5\|5ex5]], [[5ey4\|5ey4]], [[5f0x\|5f0x]], [[5f1x\|5f1x]], [[5f2r\|5f2r]]</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=5exw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exw OCA], [http://pdbe.org/5exw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exw RCSB], [http://www.ebi.ac.uk/pdbsum/5exw PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/GRP78_HUMAN GRP78_HUMAN]] Note=Autoantigen in rheumatoid arthritis.<ref>PMID:11160188</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GRP78_HUMAN GRP78_HUMAN]] Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.<ref>PMID:2294010</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	GRP78, a member of the ER stress protein family, can relocate to the surface of cancer cells, playing key roles in promoting cell proliferation and metastasis. GRP78 consists of two major functional domains: the ATPase and protein/peptide-binding domains. The protein/peptide-binding domain of cell-surface GRP78 has served as a novel functional receptor for delivering cytotoxic agents (e.g., a apoptosis-inducing peptide or taxol) across the cell membrane. Here, we report our study on the ATPase domain of GRP78 (GRP78ATPase), whose potential as a transmembrane delivery system of cytotoxic agents (e.g., ATP-based nucleotide triphosphate analogs) remains unexploited. As the binding of ligands (ATP analogs) to a receptor (GRP78ATPase) is a pre-requisite for internalization, we determined the binding affinities and modes of GRP78ATPase for ADP, ATP and several ATP analogs using surface plasmon resonance and x-ray crystallography. The tested ATP analogs contain one of the following modifications: the nitrogen at the adenine ring 7-position to a carbon atom (7-deazaATP), the oxygen at the beta-gamma bridge position to a carbon atom (AMPPCP), or the removal of the 2'-OH group (2'-deoxyATP). We found that 7-deazaATP displays an affinity and a binding mode that resemble those of ATP regardless of magnesium ion (Mg++) concentration, suggesting that GRP78 is tolerant to modifications at the 7-position. By comparison, AMPPCP's binding affinity was lower than ATP and Mg++-dependent, as the removal of Mg++ nearly abolished binding to GRP78ATPase. The AMPPCP-Mg++ structure showed evidence for the critical role of Mg++ in AMPPCP binding affinity, suggesting that while GRP78 is sensitive to modifications at the beta-gamma bridge position, these can be tolerated in the presence of Mg++. Furthermore, 2'-deoxyATP's binding affinity was significantly lower than those for all other nucleotides tested, even in the presence of Mg++. The 2'-deoxyATP structure showed the conformation of the bound nucleotide flipped out of the active site, explaining the low affinity binding to GRP78 and suggesting that the 2'-OH group is essential for the high affinity binding to GRP78. Together, our results demonstrate that GRP78ATPase possesses nucleotide specificity more relaxed than previously anticipated and can tolerate certain modifications to the nucleobase 7-position and, to a lesser extent, the beta-gamma bridging atom, thereby providing a possible atomic mechanism underlying the transmembrane transport of the ATP analogs.

-	~~Authors: Hughes, S.J~~., ~~Antoshchenko~~, T., ~~Song~~, J.H., Pizarro~~, J.~~, Park~~, H~~.W.	+	Probing the ATP Site of GRP78 with Nucleotide Triphosphate Analogs.,Hughes SJ, Antoshchenko T, Chen Y, Lu H, Pizarro JC, Park HW PLoS One. 2016 May 4;11(5):e0154862. doi: 10.1371/journal.pone.0154862., eCollection 2016. PMID:27144892<ref>PMID:27144892</ref>

-	~~Description: Crystal structure~~ of ~~human GRP78 (70kDa heat shock protein 5~~ / ~~BIP) ATPase domain in complex with 7~~-~~deaza~~-~~ATP~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5exw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Antoshchenko, T]]		[[Category: Antoshchenko, T]]
-	[[Category: ~~Song~~, J.H]]	+	[[Category: Hughes, S J]]
-	[[Category: Park, H.W]]	+	[[Category: Park, H W]]
-	~~[[Category: Hughes, S.J~~]]	+
	[[Category: Pizarro, J]]		[[Category: Pizarro, J]]
		+	[[Category: Song, J H]]
		+	[[Category: Atpase domain]]
		+	[[Category: Chaperone]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Nucleotide-binding]]

OCA at 12:21, 16 December 2015

OCA — Wed, 16 Dec 2015 12:21:13 GMT

←Older revision		Revision as of 12:21, 16 December 2015
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	The entry 5exw is ON HOLD		The entry 5exw is ON HOLD

-	Authors: Hughes, S.J., Antoshchenko, T., Song, J, Pizarro, J, Park, H	+	Authors: Hughes, S.J., Antoshchenko, T., Song, J.H., Pizarro, J., Park, H.W.

	Description: Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP		Description: Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Antoshchenko, T]]		[[Category: Antoshchenko, T]]
		+	[[Category: Song, J.H]]
		+	[[Category: Park, H.W]]
	[[Category: Hughes, S.J]]		[[Category: Hughes, S.J]]
-	[[Category: ~~Song, J,~~ Pizarro, J~~, Park, H~~]]	+	[[Category: Pizarro, J]]

OCA: Protected "5exw" [edit=sysop:move=sysop]

OCA — Wed, 02 Dec 2015 15:08:31 GMT

Protected "5exw" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:08, 2 December 2015

OCA: New page: '''Unreleased structure''' The entry 5exw is ON HOLD Authors: Hughes, S.J., Antoshchenko, T., Song, J, Pizarro, J, Park, H Description: Crystal structure of human GRP78 (70kDa heat sho...

OCA — Wed, 02 Dec 2015 15:08:30 GMT

New page: '''Unreleased structure''' The entry 5exw is ON HOLD Authors: Hughes, S.J., Antoshchenko, T., Song, J, Pizarro, J, Park, H Description: Crystal structure of human GRP78 (70kDa heat sho...

New page

'''Unreleased structure'''

The entry 5exw is ON HOLD

Authors: Hughes, S.J., Antoshchenko, T., Song, J, Pizarro, J, Park, H

Description: Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with 7-deaza-ATP
[[Category: Unreleased Structures]]
[[Category: Antoshchenko, T]]
[[Category: Hughes, S.J]]
[[Category: Song, J, Pizarro, J, Park, H]]