6l59 - Revision history

OCA at 10:51, 22 November 2023

OCA — Wed, 22 Nov 2023 10:51:39 GMT

←Older revision		Revision as of 10:51, 22 November 2023
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	==Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg and ATP binding at allosteric site and Mg, ATP binding at active site.==		==Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg and ATP binding at allosteric site and Mg, ATP binding at active site.==
-	<StructureSection load='6l59' size='340' side='right'caption='[[6l59]]' scene=''>	+	<StructureSection load='6l59' size='340' side='right'caption='[[6l59]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L59 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6L59 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6l59]] 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=6L59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L59 FirstGlance]. <br>
-	</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=6l59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l59 OCA], [~~http~~://pdbe.org/6l59 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6l59 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6l59 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6l59 ProSAT]</span></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]] 2.254Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6l59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l59 OCA], [https://pdbe.org/6l59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l59 RCSB], [https://www.ebi.ac.uk/pdbsum/6l59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l59 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/IDH3A_HUMAN IDH3A_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) is responsible for the catalytic conversion of isocitrate into alpha-ketoglutarate in the Krebs cycle. This enzyme exists as the alpha2betagamma heterotetramer composed of the alphabeta and alphagamma heterodimers. Our previous biochemical data showed that the alphagamma heterodimer and the holoenzyme can be activated by low concentrations of ATP but inhibited by high concentrations of ATP; however, the molecular mechanism was unknown. Here, we report the crystal structures of the alphagamma heterodimer with ATP binding only to the allosteric site (alpha(Mg)gamma(Mg+CIT+ATP)) and to both the allosteric site and the active site (alpha(Mg+ATP)gamma(Mg+CIT+ATP)). Structural data show that ATP at low concentrations can mimic ADP to bind to the allosteric site, which stabilizes CIT binding and leads the enzyme to adopt an active conformation, revealing why the enzyme can be activated by low concentrations of ATP. On the other hand, at high concentrations ATP is competitive with NAD for binding to the catalytic site. In addition, our biochemical data show that high concentrations of ATP promote the formation of metal ion-ATP chelates. This reduces the concentration of free metal ion available for the catalytic reaction, and thus further inhibits the enzymatic activity. The combination of these two effects accounts for the inhibition of the enzyme at high concentrations of ATP. Taken together, our structural and biochemical data reveal the molecular mechanism for the dual regulatory roles of ATP on the alphagamma heterodimer of human NAD-IDH.
		+
		+	Molecular mechanism of the dual regulatory roles of ATP on the alphagamma heterodimer of human NAD-dependent isocitrate dehydrogenase.,Sun P, Bai T, Ma T, Ding J Sci Rep. 2020 Apr 10;10(1):6225. doi: 10.1038/s41598-020-63425-6. PMID:32277159<ref>PMID:32277159</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6l59" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Isocitrate dehydrogenase 3D structures\|Isocitrate dehydrogenase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ding J]]		[[Category: Ding J]]
	[[Category: Sun P]]		[[Category: Sun P]]

OCA at 06:39, 29 April 2020

OCA — Wed, 29 Apr 2020 06:39:59 GMT

←Older revision		Revision as of 06:39, 29 April 2020
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-	'''Unreleased structure'''

-	~~The entry 6l59 is ON HOLD until Paper Publication~~	+	==Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg and ATP binding at allosteric site and Mg, ATP binding at active site.==
-		+	<StructureSection load='6l59' size='340' side='right'caption='[[6l59]]' scene=''>
-	~~Authors: Sun, P.K., Ding, J.P.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L59 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L59 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg and ATP binding at allosteric site and Mg, ATP binding at active site.	+	</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=6l59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l59 OCA], [http://pdbe.org/6l59 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l59 RCSB], [http://www.ebi.ac.uk/pdbsum/6l59 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l59 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Ding, J.P]]	+	__TOC__
-	[[Category: Sun, P.K]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ding J]]
		+	[[Category: Sun P]]

OCA at 05:02, 27 November 2019

OCA — Wed, 27 Nov 2019 05:02:32 GMT

←Older revision		Revision as of 05:02, 27 November 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6l59 is ON HOLD	+	The entry 6l59 is ON HOLD until Paper Publication

	Authors: Sun, P.K., Ding, J.P.		Authors: Sun, P.K., Ding, J.P.

OCA: Protected "6l59" [edit=sysop:move=sysop]

OCA — Wed, 30 Oct 2019 07:21:09 GMT

Protected "6l59" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:21, 30 October 2019

OCA: New page: '''Unreleased structure''' The entry 6l59 is ON HOLD Authors: Sun, P.K., Ding, J.P. Description: Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg ...

OCA — Wed, 30 Oct 2019 07:21:07 GMT

New page: '''Unreleased structure''' The entry 6l59 is ON HOLD Authors: Sun, P.K., Ding, J.P. Description: Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg ...

New page

'''Unreleased structure'''

The entry 6l59 is ON HOLD

Authors: Sun, P.K., Ding, J.P.

Description: Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with CIT, Mg and ATP binding at allosteric site and Mg, ATP binding at active site.
[[Category: Unreleased Structures]]
[[Category: Ding, J.P]]
[[Category: Sun, P.K]]