5w8i - Revision history

OCA at 14:08, 4 October 2023

OCA — Wed, 04 Oct 2023 14:08:50 GMT

←Older revision		Revision as of 14:08, 4 October 2023
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	<StructureSection load='5w8i' size='340' side='right'caption='[[5w8i]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5w8i' size='340' side='right'caption='[[5w8i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5w8i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W8I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5W8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5w8i]] 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=5W8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W8I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9YD:2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic+acid'>9YD</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.95Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9YD:2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic+acid'>9YD</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5w8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w8i OCA], [~~http~~://pdbe.org/5w8i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5w8i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5w8i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5w8i 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=5w8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w8i OCA], [https://pdbe.org/5w8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w8i RCSB], [https://www.ebi.ac.uk/pdbsum/5w8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w8i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[~~http~~://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>	+	[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[https://omim.org/entry/612933 612933]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_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: ~~L-lactate dehydrogenase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Abendroth, J]]	+	[[Category: Abendroth J]]
-	[[Category: Lukacs~~, C M]]~~	+	[[Category: Lukacs CM]]
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase inhibitor~~]]	+

OCA at 08:49, 30 September 2020

OCA — Wed, 30 Sep 2020 08:49:18 GMT

←Older revision		Revision as of 08:49, 30 September 2020
Line 1:		Line 1:

	==Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 23 and Zinc==		==Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 23 and Zinc==
-	<StructureSection load='5w8i' size='340' side='right' caption='[[5w8i]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5w8i' size='340' side='right'caption='[[5w8i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5w8i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W8I OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5W8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5w8i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W8I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W8I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9YD:2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic+acid'>9YD</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9YD:2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic+acid'>9YD</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </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=5w8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w8i OCA], [http://pdbe.org/5w8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w8i RCSB], [http://www.ebi.ac.uk/pdbsum/5w8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w8i ProSAT]</span></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=5w8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w8i OCA], [http://pdbe.org/5w8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w8i RCSB], [http://www.ebi.ac.uk/pdbsum/5w8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w8i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5w8i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5w8i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Lactate dehydrogenase 3D structures\|Lactate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: L-lactate dehydrogenase]]		[[Category: L-lactate dehydrogenase]]
		+	[[Category: Large Structures]]
	[[Category: Abendroth, J]]		[[Category: Abendroth, J]]
	[[Category: Lukacs, C M]]		[[Category: Lukacs, C M]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Oxidoreductase inhibitor]]		[[Category: Oxidoreductase inhibitor]]

OCA at 06:54, 17 January 2018

OCA — Wed, 17 Jan 2018 06:54:39 GMT

←Older revision		Revision as of 06:54, 17 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5w8i is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 23 and Zinc==
		+	<StructureSection load='5w8i' size='340' side='right' caption='[[5w8i]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5w8i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W8I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9YD:2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic+acid'>9YD</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </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=5w8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w8i OCA], [http://pdbe.org/5w8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w8i RCSB], [http://www.ebi.ac.uk/pdbsum/5w8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w8i ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report the discovery and medicinal chemistry optimization of a novel series of pyrazole-based inhibitors of human lactate dehydrogenase (LDH). Utilization of a quantitative high-throughput screening paradigm facilitated hit identification, while structure-based design and multiparameter optimization enabled the development of compounds with potent enzymatic and cell-based inhibition of LDH enzymatic activity. Lead compounds such as 63 exhibit low nM inhibition of both LDHA and LDHB, submicromolar inhibition of lactate production, and inhibition of glycolysis in MiaPaCa2 pancreatic cancer and A673 sarcoma cells. Moreover, robust target engagement of LDHA by lead compounds was demonstrated using the cellular thermal shift assay (CETSA), and drug-target residence time was determined via SPR. Analysis of these data suggests that drug-target residence time (off-rate) may be an important attribute to consider for obtaining potent cell-based inhibition of this cancer metabolism target.

-	~~Authors~~:	+	Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH).,Rai G, Brimacombe KR, Mott BT, Urban DJ, Hu X, Yang SM, Lee TD, Cheff DM, Kouznetsova J, Benavides GA, Pohida K, Kuenstner EJ, Luci DK, Lukacs CM, Davies DR, Dranow DM, Zhu H, Sulikowski G, Moore WJ, Stott GM, Flint AJ, Hall MD, Darley-Usmar VM, Neckers LM, Dang CV, Waterson AG, Simeonov A, Jadhav A, Maloney DJ J Med Chem. 2017 Nov 22;60(22):9184-9204. doi: 10.1021/acs.jmedchem.7b00941. Epub, 2017 Nov 9. PMID:29120638<ref>PMID:29120638</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5w8i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: L-lactate dehydrogenase]]
		+	[[Category: Abendroth, J]]
		+	[[Category: Lukacs, C M]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase inhibitor]]

OCA: Protected "5w8i" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:34:24 GMT

Protected "5w8i" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:34, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5w8i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 14:34:22 GMT

New page: '''Unreleased structure''' The entry 5w8i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5w8i is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]