6pay - Revision history

OCA at 07:26, 11 October 2023

2023-10-11T07:26:21Z

←Older revision		Revision as of 07:26, 11 October 2023
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	<StructureSection load='6pay' size='340' side='right'caption='[[6pay]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6pay' size='340' side='right'caption='[[6pay]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pay]] is a 4 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=6PAY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PAY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pay]] is a 4 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=6PAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PAY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 2.199Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDH1, PICD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] </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=6pay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pay OCA], [https://pdbe.org/6pay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pay RCSB], [https://www.ebi.ac.uk/pdbsum/6pay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pay 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=6pay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pay OCA], [~~http~~://pdbe.org/6pay PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pay RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pay PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pay ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN]] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:[~~http~~://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.	+	[https://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN]
	<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 6pay" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6pay" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Isocitrate dehydrogenase 3D structures\|Isocitrate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Melkonian~~, T R~~]]	+	[[Category: Melkonian TR]]
-	[[Category: Moran~~, G R~~]]	+	[[Category: Moran GR]]
-	[[Category: Roman~~, J V~~]]	+	[[Category: Roman JV]]
-	[[Category: Silvaggi~~, N R]]~~	+	[[Category: Silvaggi NR]]
-	~~[[Category: Half-sites reactivity]]~~	+
-	~~[[Category: Icdh mechanism]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Substrate complex~~]]	+

OCA at 09:37, 8 January 2020

2020-01-08T09:37:10Z

←Older revision		Revision as of 09:37, 8 January 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6pay is ~~ON HOLD until Paper~~ Publication	+	==Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity==
		+	<StructureSection load='6pay' size='340' side='right'caption='[[6pay]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pay]] is a 4 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=6PAY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PAY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDH1, PICD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] </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=6pay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pay OCA], [http://pdbe.org/6pay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pay RCSB], [http://www.ebi.ac.uk/pdbsum/6pay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pay ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN]] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human isocitrate dehydrogenase 1 (HsICDH1) is a cytoplasmic homodimeric Mg(II)-dependent enzyme that converts d-isocitrate (D-ICT) and NADP(+) to alpha-ketoglutarate (AKG), CO2, and NADPH. The active sites are formed at the subunit interface and incorporate residues from both protomers. The turnover number titrates hyperbolically from 17.5 s(-1) to a minimum of 7 s(-1) with an increasing enzyme concentration. As isolated, the enzyme adopts an inactive open conformation and binds NADPH tightly. The open conformation displaces three of the eight residues that bind D-ICT and Mg(II). Enzyme activation occurs with the addition of Mg(II) or D-ICT with a rate constant of 0.12 s(-1). The addition of both Mg(II) and D-ICT activates the enzyme with a rate constant of 0.6 s(-1) and displaces half of the bound NADPH. This indicates that HsICDH1 may have a half-site mechanism in which the active sites alternate in catalysis. The X-ray crystal structure of the half-site activated complex reveals asymmetry in the homodimer with a single NADPH bound. The structure also indicates a pseudotetramer interface that impedes the egress of NADPH consistent with the suppression of the turnover number at high enzyme concentrations. When the half-site activated form of the enzyme is reacted with NADP(+), NADPH forms with a rate constant of 204 s(-1) followed by a shift in the NADPH absorption spectrum with a rate constant of 28 s(-1). These data indicate the accumulation of two intermediate states. Once D-ICT is exhausted, HsICDH1 relaxes to the inactive open state with a rate constant of approximately 3 s(-1).

-	~~Authors~~: ~~Silvaggi, N.R~~., Melkonian, T.R.~~, Roman, J~~.V.~~, Moran, G~~.R.	+	Transient-State Analysis of Human Isocitrate Dehydrogenase I: Accounting for the Interconversion of Active and Non-Active Conformational States.,Roman JV, Melkonian TR, Silvaggi NR, Moran GR Biochemistry. 2019 Dec 31;58(52):5366-5380. doi: 10.1021/acs.biochem.9b00518., Epub 2019 Sep 10. PMID:31478653<ref>PMID:31478653</ref>

-	~~Description: Structure~~ of ~~HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation~~ of ~~half~~-~~sites reactivity~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Roman, J.V~~]]	+	<div class="pdbe-citations 6pay" style="background-color:#fffaf0;"></div>
-	[[Category: Melkonian, T.R]]	+	== References ==
-	[[Category: ~~Silvaggi~~, N.R]]	+	<references/>
-	[[Category: ~~Moran~~, G.R]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Melkonian, T R]]
		+	[[Category: Moran, G R]]
		+	[[Category: Roman, J V]]
		+	[[Category: Silvaggi, N R]]
		+	[[Category: Half-sites reactivity]]
		+	[[Category: Icdh mechanism]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Substrate complex]]

OCA at 08:55, 17 July 2019

2019-07-17T08:55:32Z

←Older revision		Revision as of 08:55, 17 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Silvaggi, N.R., Melkonian, T.R., Roman, J.V., Moran, G.R.		Authors: Silvaggi, N.R., Melkonian, T.R., Roman, J.V., Moran, G.R.
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	Description: Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity		Description: Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Silvaggi, N.R]]
	[[Category: Roman, J.V]]		[[Category: Roman, J.V]]
	[[Category: Melkonian, T.R]]		[[Category: Melkonian, T.R]]
		+	[[Category: Silvaggi, N.R]]
	[[Category: Moran, G.R]]		[[Category: Moran, G.R]]

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

2019-06-19T04:24:41Z

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

←Older revision

Revision as of 04:24, 19 June 2019

OCA: New page: '''Unreleased structure''' The entry 6pay is ON HOLD Authors: Silvaggi, N.R., Melkonian, T.R., Roman, J.V., Moran, G.R. Description: Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex ...

2019-06-19T04:24:39Z

New page: '''Unreleased structure''' The entry 6pay is ON HOLD Authors: Silvaggi, N.R., Melkonian, T.R., Roman, J.V., Moran, G.R. Description: Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex ...

New page

'''Unreleased structure'''

The entry 6pay is ON HOLD

Authors: Silvaggi, N.R., Melkonian, T.R., Roman, J.V., Moran, G.R.

Description: Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity
[[Category: Unreleased Structures]]
[[Category: Silvaggi, N.R]]
[[Category: Roman, J.V]]
[[Category: Melkonian, T.R]]
[[Category: Moran, G.R]]