7lla - Revision history

OCA at 19:38, 29 May 2024

OCA — Wed, 29 May 2024 19:38:19 GMT

←Older revision		Revision as of 19:38, 29 May 2024
Line 3:		Line 3:
	<StructureSection load='7lla' size='340' side='right'caption='[[7lla]], [[Resolution\|resolution]] 2.97Å' scene=''>		<StructureSection load='7lla' size='340' side='right'caption='[[7lla]], [[Resolution\|resolution]] 2.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[7lla]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LLA FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LLA FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>~~, ~~<scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.97Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>ACLY ([https://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=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/ATP_citrate_synthase ATP citrate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.8 2.3.3.8]~~ </~~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=7lla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lla OCA], [https://pdbe.org/7lla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lla RCSB], [https://www.ebi.ac.uk/pdbsum/7lla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lla 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=7lla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lla OCA], [https://pdbe.org/7lla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lla RCSB], [https://www.ebi.ac.uk/pdbsum/7lla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lla ProSAT]</span></td></tr>
	</table>		</table>
-	== ~~Function~~ ==	+	<div style="background-color:#fffaf0;">
-	~~[[https://www.uniprot.org/uniprot/ACLY_HUMAN ACLY_HUMAN]]~~ ATP citrate-lyase ~~is the primary enzyme responsible for the synthesis of~~ cytosolic acetyl-CoA in many ~~tissues~~. ~~Has~~ a ~~central role~~ in ~~de novo lipid synthesis~~. ~~In nervous tissue it may be involved~~ in the ~~biosynthesis~~ of ~~acetylcholine~~.<ref>PMID:~~23932781~~</ref>	+	== Publication Abstract from PubMed ==
		+	ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report cryo-EM structures of human ACLY, alone or bound to substrates or products. ACLY forms a homotetramer with a rigid citrate synthase homology (CSH) module, flanked by four flexible acetyl-CoA synthetase homology (ASH) domains; CoA is bound at the CSH-ASH interface in mutually exclusive productive or unproductive conformations. The structure of a catalytic mutant of ACLY in the presence of ATP, citrate and CoA substrates reveals a phospho-citryl-CoA intermediate in the ASH domain. ACLY with acetyl-CoA and oxaloacetate products shows the products bound in the ASH domain, with an additional oxaloacetate in the CSH domain, which could function in ACLY autoinhibition. These structures, which are supported by biochemical and biophysical data, challenge previous proposals of the ACLY catalytic mechanism and suggest additional therapeutic possibilities for ACLY-associated metabolic disorders.
		+
		+	Molecular basis for acetyl-CoA production by ATP-citrate lyase.,Wei X, Schultz K, Bazilevsky GA, Vogt A, Marmorstein R Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0351-6. doi:, 10.1038/s41594-019-0351-6. PMID:31873304<ref>PMID:31873304</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lla" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 18:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ATP citrate synthase]]
-	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Marmorstein, R]]	+	[[Category: Marmorstein R]]
-	[[Category: Wei, X]]	+	[[Category: Wei X]]
-	~~[[Category: Lyase~~]]	+

OCA at 06:33, 25 August 2021

OCA — Wed, 25 Aug 2021 06:33:25 GMT

←Older revision		Revision as of 06:33, 25 August 2021
Line 11:		Line 11:
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/ACLY_HUMAN ACLY_HUMAN]] ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.<ref>PMID:23932781</ref>		[[https://www.uniprot.org/uniprot/ACLY_HUMAN ACLY_HUMAN]] ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.<ref>PMID:23932781</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report cryo-EM structures of human ACLY, alone or bound to substrates or products. ACLY forms a homotetramer with a rigid citrate synthase homology (CSH) module, flanked by four flexible acetyl-CoA synthetase homology (ASH) domains; CoA is bound at the CSH-ASH interface in mutually exclusive productive or unproductive conformations. The structure of a catalytic mutant of ACLY in the presence of ATP, citrate and CoA substrates reveals a phospho-citryl-CoA intermediate in the ASH domain. ACLY with acetyl-CoA and oxaloacetate products shows the products bound in the ASH domain, with an additional oxaloacetate in the CSH domain, which could function in ACLY autoinhibition. These structures, which are supported by biochemical and biophysical data, challenge previous proposals of the ACLY catalytic mechanism and suggest additional therapeutic possibilities for ACLY-associated metabolic disorders.
-
-	Molecular basis for acetyl-CoA production by ATP-citrate lyase.,Wei X, Schultz K, Bazilevsky GA, Vogt A, Marmorstein R Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0351-6. doi:, 10.1038/s41594-019-0351-6. PMID:31873304<ref>PMID:31873304</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7lla" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 10:52, 28 July 2021

OCA — Wed, 28 Jul 2021 10:52:55 GMT

←Older revision		Revision as of 10:52, 28 July 2021
Line 1:		Line 1:

	==Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement)==		==Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement)==
-	<StructureSection load='7lla' size='340' side='right'caption='[[7lla]]' scene=''>	+	<StructureSection load='7lla' size='340' side='right'caption='[[7lla]], [[Resolution\|resolution]] 2.97Å' 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=7LLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LLA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lla]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LLA 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=7lla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lla OCA], [https://pdbe.org/7lla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lla RCSB], [https://www.ebi.ac.uk/pdbsum/7lla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lla 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=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACLY ([https://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'>[https://en.wikipedia.org/wiki/ATP_citrate_synthase ATP citrate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.8 2.3.3.8] </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=7lla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lla OCA], [https://pdbe.org/7lla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lla RCSB], [https://www.ebi.ac.uk/pdbsum/7lla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lla ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/ACLY_HUMAN ACLY_HUMAN]] ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.<ref>PMID:23932781</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report cryo-EM structures of human ACLY, alone or bound to substrates or products. ACLY forms a homotetramer with a rigid citrate synthase homology (CSH) module, flanked by four flexible acetyl-CoA synthetase homology (ASH) domains; CoA is bound at the CSH-ASH interface in mutually exclusive productive or unproductive conformations. The structure of a catalytic mutant of ACLY in the presence of ATP, citrate and CoA substrates reveals a phospho-citryl-CoA intermediate in the ASH domain. ACLY with acetyl-CoA and oxaloacetate products shows the products bound in the ASH domain, with an additional oxaloacetate in the CSH domain, which could function in ACLY autoinhibition. These structures, which are supported by biochemical and biophysical data, challenge previous proposals of the ACLY catalytic mechanism and suggest additional therapeutic possibilities for ACLY-associated metabolic disorders.
		+
		+	Molecular basis for acetyl-CoA production by ATP-citrate lyase.,Wei X, Schultz K, Bazilevsky GA, Vogt A, Marmorstein R Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0351-6. doi:, 10.1038/s41594-019-0351-6. PMID:31873304<ref>PMID:31873304</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lla" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[ATP-citrate synthase 3D structures\|ATP-citrate synthase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: ATP citrate synthase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Marmorstein R]]	+	[[Category: Marmorstein, R]]
-	[[Category: Wei X]]	+	[[Category: Wei, X]]
		+	[[Category: Lyase]]

OCA at 14:47, 3 March 2021

OCA — Wed, 03 Mar 2021 14:47:05 GMT

←Older revision		Revision as of 14:47, 3 March 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7lla is ON HOLD~~	+	==Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement)==
-		+	<StructureSection load='7lla' size='340' side='right'caption='[[7lla]]' scene=''>
-	~~Authors: Xuepeng, W., Ronen, M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LLA FirstGlance]. <br>
-	~~Description:~~ Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement)	+	</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=7lla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lla OCA], [https://pdbe.org/7lla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lla RCSB], [https://www.ebi.ac.uk/pdbsum/7lla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lla ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Xuepeng, W~~]]	+	__TOC__
-	[[Category: ~~Ronen, M~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Marmorstein R]]
		+	[[Category: Wei X]]

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

OCA — Wed, 10 Feb 2021 09:21:08 GMT

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

←Older revision

Revision as of 09:21, 10 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lla is ON HOLD Authors: Xuepeng, W., Ronen, M. Description: Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM m...

OCA — Wed, 10 Feb 2021 09:21:07 GMT

New page: '''Unreleased structure''' The entry 7lla is ON HOLD Authors: Xuepeng, W., Ronen, M. Description: Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM m...

New page

'''Unreleased structure'''

The entry 7lla is ON HOLD

Authors: Xuepeng, W., Ronen, M.

Description: Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement)
[[Category: Unreleased Structures]]
[[Category: Xuepeng, W]]
[[Category: Ronen, M]]