5w1l - Revision history

OCA at 08:47, 30 September 2020

OCA — Wed, 30 Sep 2020 08:47:06 GMT

←Older revision		Revision as of 08:47, 30 September 2020
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	==Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold==		==Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold==
-	<StructureSection load='5w1l' size='340' side='right' caption='[[5w1l]], [[Resolution\|resolution]] 2.88Å' scene=''>	+	<StructureSection load='5w1l' size='340' side='right'caption='[[5w1l]], [[Resolution\|resolution]] 2.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5w1l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1L OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5W1L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5w1l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W1L FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w1j\|5w1j]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w1j\|5w1j]]</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=5w1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1l OCA], [http://pdbe.org/5w1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1l RCSB], [http://www.ebi.ac.uk/pdbsum/5w1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1l 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=5w1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1l OCA], [http://pdbe.org/5w1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1l RCSB], [http://www.ebi.ac.uk/pdbsum/5w1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1l ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 5w1l" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5w1l" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thioredoxin Glutathione Reductase\|Thioredoxin Glutathione Reductase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Dai, S]]		[[Category: Dai, S]]
	[[Category: Gao, W]]		[[Category: Gao, W]]

OCA at 07:43, 22 November 2017

OCA — Wed, 22 Nov 2017 07:43:37 GMT

←Older revision		Revision as of 07:43, 22 November 2017
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-	'''Unreleased structure'''

-	~~The entry~~ 5w1l is ~~ON HOLD~~	+	==Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold==
		+	<StructureSection load='5w1l' size='340' side='right' caption='[[5w1l]], [[Resolution\|resolution]] 2.88Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5w1l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W1L FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w1j\|5w1j]]</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=5w1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1l OCA], [http://pdbe.org/5w1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1l RCSB], [http://www.ebi.ac.uk/pdbsum/5w1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1l ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	AIMS: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with AuI-MPO, a novel gold inhibitor, together with inhibition assays were performed. RESULTS: AuI-MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys519 and Cys573 in the AuI-TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys-->Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. INNOVATION: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. CONCLUSIONS: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys519 and Cys573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.

-	~~Authors: Gao~~, W., Wang, Y., ~~Dai~~, S.	+	The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).,Salinas G, Gao W, Wang Y, Bonilla M, Yu L, Novikov A, Virginio VG, Ferreira HB, Vieites M, Gladyshev VN, Gambino D, Dai S Antioxid Redox Signal. 2017 Dec 20;27(18):1491-1504. doi: 10.1089/ars.2016.6816. , Epub 2017 Jun 26. PMID:28463568<ref>PMID:28463568</ref>

-	~~Description: Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Wang, Y]]~~	+	<div class="pdbe-citations 5w1l" style="background-color:#fffaf0;"></div>
-	~~[[Category: Gao, W]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Dai, S]]		[[Category: Dai, S]]
		+	[[Category: Gao, W]]
		+	[[Category: Wang, Y]]
		+	[[Category: Antioxidant]]
		+	[[Category: Egtgr]]
		+	[[Category: Redox]]
		+	[[Category: Signaling protein]]

OCA: Protected "5w1l" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:20:31 GMT

Protected "5w1l" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:20, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5w1l is ON HOLD Authors: Gao, W., Wang, Y., Dai, S. Description: Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold [[Categ...

OCA — Wed, 27 Sep 2017 14:20:30 GMT

New page: '''Unreleased structure''' The entry 5w1l is ON HOLD Authors: Gao, W., Wang, Y., Dai, S. Description: Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold [[Categ...

New page

'''Unreleased structure'''

The entry 5w1l is ON HOLD

Authors: Gao, W., Wang, Y., Dai, S.

Description: Echinococcus granulosus thioredoxin glutathione reductas (egTGR) with Gold
[[Category: Unreleased Structures]]
[[Category: Wang, Y]]
[[Category: Gao, W]]
[[Category: Dai, S]]