6vg0 - Revision history

OCA at 08:11, 11 October 2023

OCA — Wed, 11 Oct 2023 08:11:18 GMT

←Older revision		Revision as of 08:11, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6vg0' size='340' side='right'caption='[[6vg0]], [[Resolution\|resolution]] 2.66Å' scene=''>		<StructureSection load='6vg0' size='340' side='right'caption='[[6vg0]], [[Resolution\|resolution]] 2.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vg0]] is a 3 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=6VG0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6VG0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vg0]] is a 3 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=6VG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VG0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=QWM:N~2~,N~4~-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)pyridin-2-yl]-1,3,5-triazine-2,4-diamine'>QWM</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]] 2.66Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ve1\|6ve1]], [[6vfz\|6vfz]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=QWM:N~2~,N~4~-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)pyridin-2-yl]-1,3,5-triazine-2,4-diamine'>QWM</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg0 OCA], [https://pdbe.org/6vg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vg0 RCSB], [https://www.ebi.ac.uk/pdbsum/6vg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg0 ProSAT]</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=6vg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg0 OCA], [~~http~~://pdbe.org/6vg0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vg0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vg0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg0 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 ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6vg0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6vg0" 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: Jin, L]]	+	[[Category: Jin L]]
-	[[Category: Padyana, A]]	+	[[Category: Padyana A]]
-	~~[[Category: Cytosolic nadp-isocitrate dehydrogenase]]~~	+
-	~~[[Category: Idh]]~~	+
-	~~[[Category: Idp]]~~	+
-	~~[[Category: Oxalosuccinate decarboxylase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 07:23, 4 March 2020

OCA — Wed, 04 Mar 2020 07:23:47 GMT

←Older revision		Revision as of 07:23, 4 March 2020
Line 3:		Line 3:
	<StructureSection load='6vg0' size='340' side='right'caption='[[6vg0]], [[Resolution\|resolution]] 2.66Å' scene=''>		<StructureSection load='6vg0' size='340' side='right'caption='[[6vg0]], [[Resolution\|resolution]] 2.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vg0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VG0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vg0]] is a 3 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=6VG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VG0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=QWM:N~2~,N~4~-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)pyridin-2-yl]-1,3,5-triazine-2,4-diamine'>QWM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=QWM:N~2~,N~4~-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)pyridin-2-yl]-1,3,5-triazine-2,4-diamine'>QWM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ve1\|6ve1]], [[6vfz\|6vfz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ve1\|6ve1]], [[6vfz\|6vfz]]</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=6vg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg0 OCA], [http://pdbe.org/6vg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg0 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=6vg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg0 OCA], [http://pdbe.org/6vg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg0 ProSAT]</span></td></tr>
Line 11:		Line 12:
	== 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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibitors of mutant isocitrate dehydrogenase (mIDH) 1 and 2 cancer-associated enzymes prevent the accumulation of the oncometabolite d-2-hydroxyglutarate (2-HG) and are under clinical investigation for the treatment of several cancers harboring an IDH mutation. Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. X-ray cocrystal structures allowed us to characterize the compound binding site, leading to an understanding of the dual mutant inhibition. Furthermore, vorasidenib penetrates the brain of several preclinical species and inhibits 2-HG production in glioma tissue by >97% in an orthotopic glioma mouse model. Vorasidenib represents a novel dual mIDH1/2 inhibitor and is currently in clinical development for the treatment of low-grade mIDH glioma.
		+
		+	Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma.,Konteatis Z, Artin E, Nicolay B, Straley K, Padyana AK, Jin L, Chen Y, Narayaraswamy R, Tong S, Wang F, Zhou D, Cui D, Cai Z, Luo Z, Fang C, Tang H, Lv X, Nagaraja R, Yang H, Su SM, Sui Z, Dang L, Yen K, Popovici-Muller J, Codega P, Campos C, Mellinghoff IK, Biller SA ACS Med Chem Lett. 2020 Jan 22;11(2):101-107. doi:, 10.1021/acsmedchemlett.9b00509. eCollection 2020 Feb 13. PMID:32071674<ref>PMID:32071674</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vg0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Jin, L]]		[[Category: Jin, L]]

OCA at 08:18, 5 February 2020

OCA — Wed, 05 Feb 2020 08:18:25 GMT

←Older revision		Revision as of 08:18, 5 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6vg0 is ~~ON HOLD until Paper Publication~~	+	==CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC ISOCITRATE DEHYDROGENASE (IDH1) R132H MUTANT IN COMPLEX WITH NADPH and AGI-15056==
-		+	<StructureSection load='6vg0' size='340' side='right'caption='[[6vg0]], [[Resolution\|resolution]] 2.66Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6vg0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VG0 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=QWM:N~2~,N~4~-bis[(1R)-1-cyclopropylethyl]-6-[6-(trifluoromethyl)pyridin-2-yl]-1,3,5-triazine-2,4-diamine'>QWM</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ve1\|6ve1]], [[6vfz\|6vfz]]</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=6vg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg0 OCA], [http://pdbe.org/6vg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg0 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.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Jin, L]]
		+	[[Category: Padyana, A]]
		+	[[Category: Cytosolic nadp-isocitrate dehydrogenase]]
		+	[[Category: Idh]]
		+	[[Category: Idp]]
		+	[[Category: Oxalosuccinate decarboxylase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA: Protected "6vg0" [edit=sysop:move=sysop]

OCA — Wed, 22 Jan 2020 14:23:38 GMT

Protected "6vg0" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:23, 22 January 2020

OCA: New page: '''Unreleased structure''' The entry 6vg0 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jan 2020 14:23:37 GMT

New page: '''Unreleased structure''' The entry 6vg0 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6vg0 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]