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| <StructureSection load='6hxi' size='340' side='right'caption='[[6hxi]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6hxi' size='340' side='right'caption='[[6hxi]], [[Resolution|resolution]] 2.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6hxi]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35969_[[methanosaeta_concilii]] Atcc 35969 [[methanosaeta concilii]]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HXI FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6hxi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanothrix_soehngenii Methanothrix soehngenii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HXI FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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]] 2.1Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ATP_citrate_synthase ATP citrate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.8 2.3.3.8] </span></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=6hxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hxi OCA], [http://pdbe.org/6hxi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hxi RCSB], [http://www.ebi.ac.uk/pdbsum/6hxi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hxi 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=6hxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hxi OCA], [https://pdbe.org/6hxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hxi RCSB], [https://www.ebi.ac.uk/pdbsum/6hxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hxi ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/A0A0W8FB26_9ZZZZ A0A0W8FB26_9ZZZZ] |
| Across different kingdoms of life, ATP citrate lyase (ACLY, also known as ACL) catalyses the ATP-dependent and coenzyme A (CoA)-dependent conversion of citrate, a metabolic product of the Krebs cycle, to oxaloacetate and the high-energy biosynthetic precursor acetyl-CoA(1). The latter fuels pivotal biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine(2), and the acetylation of histones and proteins(3,4). In autotrophic prokaryotes, ACLY is a hallmark enzyme of the reverse Krebs cycle (also known as the reductive tricarboxylic acid cycle), which fixates two molecules of carbon dioxide in acetyl-CoA(5,6). In humans, ACLY links carbohydrate and lipid metabolism and is strongly expressed in liver and adipose tissue(1) and in cholinergic neurons(2,7). The structural basis of the function of ACLY remains unknown. Here we report high-resolution crystal structures of bacterial, archaeal and human ACLY, and use distinct substrate-bound states to link the conformational plasticity of ACLY to its multistep catalytic itinerary. Such detailed insights will provide the framework for targeting human ACLY in cancer(8-11) and hyperlipidaemia(12,13). Our structural studies also unmask a fundamental evolutionary relationship that links citrate synthase, the first enzyme of the oxidative Krebs cycle, to an ancestral tetrameric citryl-CoA lyase module that operates in the reverse Krebs cycle. This molecular transition marked a key step in the evolution of metabolism on Earth.
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| Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle.,Verschueren KHG, Blanchet C, Felix J, Dansercoer A, De Vos D, Bloch Y, Van Beeumen J, Svergun D, Gutsche I, Savvides SN, Verstraete K Nature. 2019 Apr 3. pii: 10.1038/s41586-019-1095-5. doi:, 10.1038/s41586-019-1095-5. PMID:30944476<ref>PMID:30944476</ref>
| | ==See Also== |
| | | *[[ATP-citrate synthase 3D structures|ATP-citrate synthase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| | *[[Succinyl-CoA synthetase 3D structures|Succinyl-CoA synthetase 3D structures]] |
| </div>
| |
| <div class="pdbe-citations 6hxi" style="background-color:#fffaf0;"></div>
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| == References ==
| |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: ATP citrate synthase]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Verschueren, K]] | | [[Category: Methanothrix soehngenii]] |
| [[Category: Verstraete, K]] | | [[Category: Verschueren K]] |
| [[Category: Acetyl-coa]] | | [[Category: Verstraete K]] |
| [[Category: Atp citrate lyase]]
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| [[Category: Central metabolism]]
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| [[Category: Citrate shuttle]]
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| [[Category: Citryl-coa]]
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| [[Category: Lipogenesis]]
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| [[Category: Lyase]]
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| [[Category: Rtca cycle]]
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