7edz - Revision history

OCA at 16:51, 29 November 2023

2023-11-29T16:51:18Z

←Older revision		Revision as of 16:51, 29 November 2023
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	<StructureSection load='7edz' size='340' side='right'caption='[[7edz]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='7edz' size='340' side='right'caption='[[7edz]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7edz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EDZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7edz]] 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=7EDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EDZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1O:4-[[(2R)-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butanoyl]amino]butanoic+acid'>J1O</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.95Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphopantothenate--cysteine_ligase_(ATP) Phosphopantothenate--cysteine ligase (ATP)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.51 6.3.2.51] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1O:4-[[(2R)-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butanoyl]amino]butanoic+acid'>J1O</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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'>[https://proteopedia.org/fgij/fg.htm?mol=7edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7edz OCA], [https://pdbe.org/7edz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7edz RCSB], [https://www.ebi.ac.uk/pdbsum/7edz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7edz 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=7edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7edz OCA], [https://pdbe.org/7edz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7edz RCSB], [https://www.ebi.ac.uk/pdbsum/7edz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7edz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PPCS_HUMAN PPCS_HUMAN]] Catalyzes the first step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine.<ref>PMID:11923312</ref> <ref>PMID:12906824</ref>	+	[https://www.uniprot.org/uniprot/PPCS_HUMAN PPCS_HUMAN] Catalyzes the first step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine.<ref>PMID:11923312</ref> <ref>PMID:12906824</ref>
	<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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anand, R]]	+	[[Category: Anand R]]
-	[[Category: Mostert~~, K J~~]]	+	[[Category: Mostert KJ]]
-	[[Category: Sharma, N]]	+	[[Category: Sharma N]]
-	[[Category: Strauss, E]]	+	[[Category: Strauss E]]
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Phosphopantothenoylcysteine synthetase~~]]	+

OCA at 10:53, 16 February 2022

2022-02-16T10:53:56Z

←Older revision		Revision as of 10:53, 16 February 2022
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	==Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP==		==Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP==
-	<StructureSection load='7edz' size='340' side='right'caption='[[7edz]]' scene=''>	+	<StructureSection load='7edz' size='340' side='right'caption='[[7edz]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EDZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7edz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EDZ FirstGlance]. <br>
-	</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=7edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7edz OCA], [https://pdbe.org/7edz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7edz RCSB], [https://www.ebi.ac.uk/pdbsum/7edz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7edz ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1O:4-[[(2R)-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butanoyl]amino]butanoic+acid'>J1O</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphopantothenate--cysteine_ligase_(ATP) Phosphopantothenate--cysteine ligase (ATP)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.51 6.3.2.51] </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=7edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7edz OCA], [https://pdbe.org/7edz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7edz RCSB], [https://www.ebi.ac.uk/pdbsum/7edz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7edz ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/PPCS_HUMAN PPCS_HUMAN]] Catalyzes the first step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine.<ref>PMID:11923312</ref> <ref>PMID:12906824</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The pantothenate analogue hopantenate (HoPan) is widely used as a modulator of coenzyme A (CoA) levels in cell biology and disease models horizontal line especially for pantothenate kinase associated neurodegeneration (PKAN), a genetic disease rooted in impaired CoA metabolism. This use of HoPan was based on reports that it inhibits pantothenate kinase (PanK), the first enzyme of CoA biosynthesis. Using a combination of in vitro enzyme kinetic studies, crystal structure analysis, and experiments in a typical PKAN cell biology model, we demonstrate that instead of inhibiting PanK, HoPan relies on it for metabolic activation. Once phosphorylated, HoPan inhibits the next enzyme in the CoA pathway horizontal line phosphopantothenoylcysteine synthetase (PPCS) horizontal line through formation of a nonproductive substrate complex. Moreover, the obtained structure of the human PPCS in complex with the inhibitor and activating nucleotide analogue provides new insights into the catalytic mechanism of PPCS enzymes horizontal line including the elusive binding mode for cysteine horizontal line and reveals the functional implications of mutations in the human PPCS that have been linked to severe dilated cardiomyopathy. Taken together, this study demonstrates that the molecular mechanism of action of HoPan is more complex than previously thought, suggesting that the results of studies in which it is used as a tool compound must be interpreted with care. Moreover, our findings provide a clear framework for evaluating the various factors that contribute to the potency of CoA-directed inhibitors, one that will prove useful in the future rational development of potential therapies of both human genetic and infectious diseases.
		+
		+	The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity.,Mostert KJ, Sharma N, van der Zwaag M, Staats R, Koekemoer L, Anand R, Sibon OCM, Strauss E ACS Chem Biol. 2021 Nov 19;16(11):2401-2414. doi: 10.1021/acschembio.1c00535., Epub 2021 Sep 28. PMID:34582681<ref>PMID:34582681</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7edz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anand R]]	+	[[Category: Anand, R]]
-	[[Category: Mostert KJ]]	+	[[Category: Mostert, K J]]
-	[[Category: Sharma N]]	+	[[Category: Sharma, N]]
-	[[Category: Strauss E]]	+	[[Category: Strauss, E]]
		+	[[Category: Ligase]]
		+	[[Category: Phosphopantothenoylcysteine synthetase]]

OCA at 12:34, 24 November 2021

2021-11-24T12:34:27Z

←Older revision		Revision as of 12:34, 24 November 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7edz ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP==
-		+	<StructureSection load='7edz' size='340' side='right'caption='[[7edz]]' scene=''>
-	~~Authors~~: ~~Sharma~~, N., ~~Mostert~~, K.J.~~, Strauss, E~~., ~~Anand~~, R.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EDZ FirstGlance]. <br>
-	~~Description: Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP~~	+	</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=7edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7edz OCA], [https://pdbe.org/7edz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7edz RCSB], [https://www.ebi.ac.uk/pdbsum/7edz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7edz ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Sharma, N~~]]	+	__TOC__
-	[[Category: Mostert~~, K.J~~]]	+	</StructureSection>
-	[[Category: ~~Anand, R~~]]	+	[[Category: Large Structures]]
-	[[Category: Strauss, E]]	+	[[Category: Anand R]]
		+	[[Category: Mostert KJ]]
		+	[[Category: Sharma N]]
		+	[[Category: Strauss E]]

OCA at 05:33, 14 April 2021

2021-04-14T05:33:51Z

←Older revision		Revision as of 05:33, 14 April 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7edz is ON HOLD	+	The entry 7edz is ON HOLD until Paper Publication

	Authors: Sharma, N., Mostert, K.J., Strauss, E., Anand, R.		Authors: Sharma, N., Mostert, K.J., Strauss, E., Anand, R.

OCA: Protected "7edz" [edit=sysop:move=sysop]

2021-03-24T05:25:17Z

Protected "7edz" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:25, 24 March 2021

OCA: New page: '''Unreleased structure''' The entry 7edz is ON HOLD Authors: Sharma, N., Mostert, K.J., Strauss, E., Anand, R. Description: Crystal Structure of human PPCS in complex with P-HoPan and...

2021-03-24T05:25:16Z

New page: '''Unreleased structure''' The entry 7edz is ON HOLD Authors: Sharma, N., Mostert, K.J., Strauss, E., Anand, R. Description: Crystal Structure of human PPCS in complex with P-HoPan and...

New page

'''Unreleased structure'''

The entry 7edz is ON HOLD

Authors: Sharma, N., Mostert, K.J., Strauss, E., Anand, R.

Description: Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP
[[Category: Unreleased Structures]]
[[Category: Sharma, N]]
[[Category: Mostert, K.J]]
[[Category: Anand, R]]
[[Category: Strauss, E]]