6rj2 - Revision history

OCA at 12:21, 24 January 2024

2024-01-24T12:21:27Z

←Older revision		Revision as of 12:21, 24 January 2024
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	<StructureSection load='6rj2' size='340' side='right'caption='[[6rj2]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6rj2' size='340' side='right'caption='[[6rj2]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6rj2]] 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=6RJ2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6RJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rj2]] 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=6RJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RJ2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K52:~{N}-[(1~{R})-1-[4-(ethanoylsulfamoyl)phenyl]ethyl]-2-methyl-5-phenyl-pyrazole-3-carboxamide'>K52</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PHGDH, PGDH3 ([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=K52:~{N}-[(1~{R})-1-[4-(ethanoylsulfamoyl)phenyl]ethyl]-2-methyl-5-phenyl-pyrazole-3-carboxamide'>K52</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rj2 OCA], [~~http~~://pdbe.org/6rj2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6rj2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6rj2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6rj2 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=6rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rj2 OCA], [https://pdbe.org/6rj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rj2 RCSB], [https://www.ebi.ac.uk/pdbsum/6rj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rj2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[~~http~~://omim.org/entry/601815 601815]]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.	+	[https://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[https://omim.org/entry/601815 601815]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6rj2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6rj2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoglycerate dehydrogenase\|Phosphoglycerate dehydrogenase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bader, G]]	+	[[Category: Bader G]]
-	[[Category: Wolkerstorfer, B]]	+	[[Category: Wolkerstorfer B]]
-	[[Category: Zoephel, A]]	+	[[Category: Zoephel A]]
-	~~[[Category: Dehydrogenase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Protein-ligand complex~~]]	+

OCA at 17:33, 14 August 2019

2019-08-14T17:33:56Z

←Older revision		Revision as of 17:33, 14 August 2019
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	<StructureSection load='6rj2' size='340' side='right'caption='[[6rj2]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6rj2' size='340' side='right'caption='[[6rj2]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6rj2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rj2]] 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=6RJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RJ2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K52:~{N}-[(1~{R})-1-[4-(ethanoylsulfamoyl)phenyl]ethyl]-2-methyl-5-phenyl-pyrazole-3-carboxamide'>K52</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K52:~{N}-[(1~{R})-1-[4-(ethanoylsulfamoyl)phenyl]ethyl]-2-methyl-5-phenyl-pyrazole-3-carboxamide'>K52</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PHGDH, PGDH3 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rj2 OCA], [http://pdbe.org/6rj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rj2 RCSB], [http://www.ebi.ac.uk/pdbsum/6rj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rj2 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=6rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rj2 OCA], [http://pdbe.org/6rj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rj2 RCSB], [http://www.ebi.ac.uk/pdbsum/6rj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rj2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[http://omim.org/entry/601815 601815]]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.		[[http://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[http://omim.org/entry/601815 601815]]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate limiting enzyme in the serine synthesis pathway (SSP) in humans. It converts glycolysis derived 3-phosphoglycerate to 3-phosphopyruvate in a NADH/NAD(+)-dependent oxidation reaction. Herein we report the discovery of BI-4916, a prodrug of the NADH/NAD(+)-competitive PHGDH inhibitor BI-4924 which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening (FBS) a subsequent hit optimization using structure based drug design (SBDD) was conducted to deliver a single digit nanomolar lead series and to improve potency by six orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD(+).
		+
		+	Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis.,Weinstabl H, Treu M, Rinnenthal J, Zahn S, Ettmayer P, Bader G, Dahmann G, Kessler D, Rumpel K, Mischerikow N, Savarese F, Gerstberger T, Mayer M, Zoephel A, Schnitzer R, Sommergruber W, Martinelli P, Arnhof H, Peric Simov B, Hofbauer KS, Garavel G, Scherbantin Y, Mitzner S, Fett T, Scholz G, Bruchhaus J, Burkard M, Kousek R, Ciftci T, Sharps B, Schrenk A, Harrer C, Haering D, Wolkerstorfer B, Zhang X, Lv X, Du A, Li D, Li Y, Quant J, Pearson M, McConnell DB J Med Chem. 2019 Jul 31. doi: 10.1021/acs.jmedchem.9b00718. PMID:31365252<ref>PMID:31365252</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6rj2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bader, G]]		[[Category: Bader, G]]

OCA at 06:06, 7 August 2019

2019-08-07T06:06:00Z

←Older revision		Revision as of 06:06, 7 August 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6rj2 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of PHGDH in complex with compound 40==
-		+	<StructureSection load='6rj2' size='340' side='right'caption='[[6rj2]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6rj2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RJ2 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K52:~{N}-[(1~{R})-1-[4-(ethanoylsulfamoyl)phenyl]ethyl]-2-methyl-5-phenyl-pyrazole-3-carboxamide'>K52</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rj2 OCA], [http://pdbe.org/6rj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rj2 RCSB], [http://www.ebi.ac.uk/pdbsum/6rj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rj2 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/SERA_HUMAN SERA_HUMAN]] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:[http://omim.org/entry/601815 601815]]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bader, G]]
		+	[[Category: Wolkerstorfer, B]]
		+	[[Category: Zoephel, A]]
		+	[[Category: Dehydrogenase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Protein-ligand complex]]

OCA at 08:18, 10 May 2019

2019-05-10T08:18:23Z

←Older revision		Revision as of 08:18, 10 May 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6rj2 is ON HOLD	+	The entry 6rj2 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6rj2" [edit=sysop:move=sysop]

2019-05-01T07:26:59Z

Protected "6rj2" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:26, 1 May 2019

OCA: New page: '''Unreleased structure''' The entry 6rj2 is ON HOLD Authors: Description: Category: Unreleased Structures

2019-05-01T07:26:57Z

New page: '''Unreleased structure''' The entry 6rj2 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6rj2 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]