3map - Revision history

OCA at 10:41, 16 August 2023

2023-08-16T10:41:37Z

← Older revision		Revision as of 10:41, 16 August 2023
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	<StructureSection load='3map' size='340' side='right'caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3map' size='340' side='right'caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3map]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3map]] 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=3MAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MAP FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>~~, ~~<scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 2.8Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em~~;~~'>[[3mar\|3mar]], [[3mas\|3mas]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>IDH1, PICD ([https://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'>[https~~:~~//en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(~~NADP(+~~)) Isocitrate dehydrogenase (NADP(~~+~~))], with EC number [https://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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [https://pdbe.org/3map PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [https://www.ebi.ac.uk/pdbsum/3map PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3map 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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [https://pdbe.org/3map PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [https://www.ebi.ac.uk/pdbsum/3map PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3map ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[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.		[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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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ding, J]]		[[Category: Ding J]]
	[[Category: Peng, Y]]		[[Category: Peng Y]]
	[[Category: Yang, B]]		[[Category: Yang B]]
	~~[[Category: Isocitrate dehydrogenase]]~~
	~~[[Category: Nicotinamide adenine dinucleotide phosphate]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: Rossmann fold~~]]

OCA at 07:54, 10 November 2021

2021-11-10T07:54:28Z

← Older revision		Revision as of 07:54, 10 November 2021
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	==Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate==		==Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate==
	<StructureSection load='3map' size='340' side='right' caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3map' size='340' side='right'caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3map]] 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=3MAP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3MAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3map]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MAP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mar\|3mar]], [[3mas\|3mas]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3mar\|3mar]], [[3mas\|3mas]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDH1, PICD ([https://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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [https://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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [~~http~~://pdbe.org/3map PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3map PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3map 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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [https://pdbe.org/3map PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [https://www.ebi.ac.uk/pdbsum/3map PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3map 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.
	<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 3map" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3map" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Isocitrate dehydrogenase 3D structures\|Isocitrate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Ding, J]]		[[Category: Ding, J]]
	[[Category: Peng, Y]]		[[Category: Peng, Y]]

OCA at 08:08, 8 November 2017

2017-11-08T08:08:54Z

← Older revision		Revision as of 08:08, 8 November 2017
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	</div>		</div>
	<div class="pdbe-citations 3map" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3map" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Isocitrate dehydrogenase\|Isocitrate dehydrogenase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:58, 5 August 2016

2016-08-05T10:58:13Z

← Older revision		Revision as of 10:58, 5 August 2016
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	==Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate==		==Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate==
	<StructureSection load='3map' size='340' side='right' caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3map' size='340' side='right' caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>
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	<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='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='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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [http://www.ebi.ac.uk/pdbsum/3map 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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [http://pdbe.org/3map PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [http://www.ebi.ac.uk/pdbsum/3map PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3map ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	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 3map" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 18:13, 25 December 2014

2014-12-25T18:13:50Z

← Older revision		Revision as of 18:13, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3map]] 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=3MAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3map]] 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=3MAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MAP FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mar\|3mar]], [[3mas\|3mas]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mar\|3mar]], [[3mas\|3mas]]</td></tr>
	<tr><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='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><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [http://www.ebi.ac.uk/pdbsum/3map 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=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [http://www.ebi.ac.uk/pdbsum/3map PDBsum]</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.		[[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.
	~~== Function ==~~

	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H.,Yang B, Zhong C, Peng Y, Lai Z, Ding J Cell Res. 2010 Nov;20(11):1188-200. Epub 2010 Oct 26. PMID:20975740<ref>PMID:20975740</ref>		Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H.,Yang B, Zhong C, Peng Y, Lai Z, Ding J Cell Res. 2010 Nov;20(11):1188-200. Epub 2010 Oct 26. PMID:20975740<ref>PMID:20975740</ref>

	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>

			==See Also==
			*[[Isocitrate dehydrogenase\|Isocitrate dehydrogenase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Ding, J.]]		[[Category: Ding, J]]
	[[Category: Peng, Y.]]		[[Category: Peng, Y]]
	[[Category: Yang, B.]]		[[Category: Yang, B]]
	[[Category: Isocitrate dehydrogenase]]		[[Category: Isocitrate dehydrogenase]]
	[[Category: Nicotinamide adenine dinucleotide phosphate]]		[[Category: Nicotinamide adenine dinucleotide phosphate]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Rossmann fold]]		[[Category: Rossmann fold]]

OCA at 06:52, 21 May 2014

2014-05-21T06:52:48Z

← Older revision		Revision as of 06:52, 21 May 2014
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	~~{{STRUCTURE_3map\| PDB=3map \| SCENE= }}~~		==Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate==
	===Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate===		<StructureSection load='3map' size='340' side='right' caption='[[3map]], [[Resolution\|resolution]] 2.80Å' scene=''>
	~~{{ABSTRACT_PUBMED_20975740}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3map]] 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=3MAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MAP FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3mar\|3mar]], [[3mas\|3mas]]</td></tr>
			<tr><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><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3map OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3map RCSB], [http://www.ebi.ac.uk/pdbsum/3map PDBsum]</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.		[[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.
			== Function ==

	==~~About this Structure~~==		<div style="background-color:#fffaf0;">
	~~[[3map]]~~ is a 2 ~~chain structure~~ with ~~sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information~~ is ~~available~~ from ~~[http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA]~~.		== Publication Abstract from PubMed ==
			Human cytosolic NADP-IDH (IDH1) has recently been found to be involved in tumorigenesis. Notably, the tumor-derived IDH1 mutations identified so far mainly occur at Arg132, and mutation R132H is the most prevalent one. This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting alpha-ketoglutarate (alphaKG) to 2-hydroxyglutarate. Here, we report the structures of the R132H mutant IDH1 with and without isocitrate (ICT) bound. The structural data together with mutagenesis and biochemical data reveal a previously undefined initial ICT-binding state and demonstrate that IDH activity requires a conformational change to a closed pre-transition state. Arg132 plays multiple functional roles in the catalytic reaction; in particular, the R132H mutation hinders the conformational changes from the initial ICT-binding state to the pre-transition state, leading to the impairment of the IDH activity. Our results describe for the first time that there is an intermediate conformation that corresponds to an initial ICT-binding state and that the R132H mutation can trap the enzyme in this conformation, therefore shedding light on the molecular mechanism of the "off switch" of the potentially tumor-suppressive IDH activity. Furthermore, we proved the necessity of Tyr139 for the gained alphaKG reduction activity and propose that Tyr139 may play a vital role by compensating the increased negative charge on the C2 atom of alphaKG during the transfer of a hydride anion from NADPH to alphaKG, which provides new insights into the mechanism of the "on switch" of the hypothetically oncogenic reduction activity of IDH1 by this mutation.

	~~==See Also==~~		Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H.,Yang B, Zhong C, Peng Y, Lai Z, Ding J Cell Res. 2010 Nov;20(11):1188-200. Epub 2010 Oct 26. PMID:20975740<ref>PMID:20975740</ref>
	*[[Isocitrate dehydrogenase\|Isocitrate dehydrogenase]]

	==~~Reference~~==		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group="xtra">PMID:020975740</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>
	[[Category: ~~Homo sapiens~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Human]]
	[[Category: Ding, J.]]		[[Category: Ding, J.]]
	[[Category: Peng, Y.]]		[[Category: Peng, Y.]]

OCA at 20:49, 24 March 2013

2013-03-24T20:49:16Z

← Older revision		Revision as of 20:49, 24 March 2013
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	~~[[Image:3map.png\|left\|200px]]~~

	{{STRUCTURE_3map\| PDB=3map \| SCENE= }}		{{STRUCTURE_3map\| PDB=3map \| SCENE= }}

	===Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate===		===Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate===
			{{ABSTRACT_PUBMED_20975740}}

	~~{{ABSTRACT_PUBMED_20975740}}~~		==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.

	==About this Structure==		==About this Structure==
Line 14:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:020975740</ref><references group="xtra"/>		<ref group="xtra">PMID:020975740</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ding, J.]]		[[Category: Ding, J.]]

OCA at 19:51, 20 October 2012

2012-10-20T19:51:02Z

← Older revision		Revision as of 19:51, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[3map]] is a 2 chain structure ~~of [[Isocitrate dehydrogenase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA].		[[3map]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA].

	==See Also==		==See Also==

OCA: Protected "3map" [edit=sysop:move=sysop]

2012-07-27T08:40:50Z

Protected "3map" [edit=sysop:move=sysop]

← Older revision	Revision as of 08:40, 27 July 2012
(No difference)

OCA at 08:40, 27 July 2012

2012-07-27T08:40:47Z

← Older revision		Revision as of 08:40, 27 July 2012
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	~~{{Seed}}~~		[[Image:3map.png\|left\|200px]]
	[[Image:3map.~~jpg~~\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3map", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3map\| PDB=3map \| SCENE= }}		{{STRUCTURE_3map\| PDB=3map \| SCENE= }}

	===Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate===		===Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_20975740}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 20975740 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_20975740}}		{{ABSTRACT_PUBMED_20975740}}

	==About this Structure==		==About this Structure==
	~~3MAP~~ is a 2 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA].		[[3map]] is a 2 chain structure of [[Isocitrate dehydrogenase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MAP OCA].

			==See Also==
			*[[Isocitrate dehydrogenase\|Isocitrate dehydrogenase]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~20975740~~</ref><references group="xtra"/>		<ref group="xtra">PMID:020975740</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ding, J.]]		[[Category: Ding, J.]]
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	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Rossmann fold]]		[[Category: Rossmann fold]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 10 06:48:45 2010''~~