6bkz - Revision history

OCA at 14:44, 4 October 2023

OCA — Wed, 04 Oct 2023 14:44:46 GMT

←Older revision		Revision as of 14:44, 4 October 2023
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	==Novel Modes of Inhibition of Wild-Type IDH1: Non-equivalent Allosteric Inhibition with Cmpd3==		==Novel Modes of Inhibition of Wild-Type IDH1: Non-equivalent Allosteric Inhibition with Cmpd3==
-	<StructureSection load='6bkz' size='340' side='right' caption='[[6bkz]], [[Resolution\|resolution]] 2.01Å' scene=''>	+	<StructureSection load='6bkz' size='340' side='right'caption='[[6bkz]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bkz]] 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=6BKZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BKZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bkz]] 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=6BKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BKZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DWM:(7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide'>DWM</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]] 2.01Å</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=DWM:(7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide'>DWM</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bkz OCA], [https://pdbe.org/6bkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bkz RCSB], [https://www.ebi.ac.uk/pdbsum/6bkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bkz 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=6bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bkz OCA], [~~http~~://pdbe.org/6bkz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bkz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bkz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bkz 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 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6bkz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6bkz" 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: ~~Jakob, C G~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Qiu, W~~]]	+	[[Category: Jakob CG]]
-	[[Category: ~~Dehydrogenase]]~~	+	[[Category: Qiu W]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 06:33, 22 August 2018

OCA — Wed, 22 Aug 2018 06:33:05 GMT

←Older revision		Revision as of 06:33, 22 August 2018
Line 3:		Line 3:
	<StructureSection load='6bkz' size='340' side='right' caption='[[6bkz]], [[Resolution\|resolution]] 2.01Å' scene=''>		<StructureSection load='6bkz' size='340' side='right' caption='[[6bkz]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bkz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BKZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bkz]] 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=6BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BKZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DWM:(7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide'>DWM</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"><scene name='pdbligand=DWM:(7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide'>DWM</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 ([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=6bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bkz OCA], [http://pdbe.org/6bkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bkz RCSB], [http://www.ebi.ac.uk/pdbsum/6bkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bkz 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=6bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bkz OCA], [http://pdbe.org/6bkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bkz RCSB], [http://www.ebi.ac.uk/pdbsum/6bkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bkz ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Jakob, C G]]		[[Category: Jakob, C G]]
	[[Category: Qiu, W]]		[[Category: Qiu, W]]

OCA at 07:13, 25 July 2018

OCA — Wed, 25 Jul 2018 07:13:40 GMT

←Older revision		Revision as of 07:13, 25 July 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6bkz is ~~ON HOLD until Paper~~ Publication	+	==Novel Modes of Inhibition of Wild-Type IDH1: Non-equivalent Allosteric Inhibition with Cmpd3==
		+	<StructureSection load='6bkz' size='340' side='right' caption='[[6bkz]], [[Resolution\|resolution]] 2.01Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6bkz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BKZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DWM:(7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide'>DWM</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bkz OCA], [http://pdbe.org/6bkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bkz RCSB], [http://www.ebi.ac.uk/pdbsum/6bkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bkz 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 ==
		+	IDH1 plays a critical role in a number of metabolic processes and serves as a key source of cytosolic NADPH under conditions of cellular stress. However, few inhibitors of wild-type IDH1 have been reported. Here we present the discovery and biochemical characterization of two novel inhibitors of wild-type IDH1. In addition, we present the first ligand-bound crystallographic characterization of these novel small molecule IDH1 binding pockets. Importantly, the NADPH competitive ,-unsaturated enone 1 makes a unique covalent linkage through active site H315. As few small molecules have been shown to covalently react with histidine residues, these data support the potential utility of an underutilized strategy for reversible covalent small molecule design.

-	~~Authors~~:	+	Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315.,Jakob CG, Upadhyay AK, Donner PL, Nicholl E, Addo SN, Qiu W, Ling C, Gopalakrishnan SM, Torrent M, Cepa SP, Shanley J, Shoemaker AR, Sun CC, Vasudevan A, Woller KR, Shotwell JB, Shaw B, Bian Z, Hutti JE J Med Chem. 2018 Jul 13. doi: 10.1021/acs.jmedchem.8b00305. PMID:30004704<ref>PMID:30004704</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6bkz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Jakob, C G]]
		+	[[Category: Qiu, W]]
		+	[[Category: Dehydrogenase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 06:03, 6 December 2017

OCA — Wed, 06 Dec 2017 06:03:21 GMT

←Older revision		Revision as of 06:03, 6 December 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 15 Nov 2017 06:26:02 GMT

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

←Older revision

Revision as of 06:26, 15 November 2017

OCA: New page: '''Unreleased structure''' The entry 6bkz is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 15 Nov 2017 06:26:00 GMT

New page: '''Unreleased structure''' The entry 6bkz is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6bkz is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]