View source for 6qfb


==Structure of the human ATP citrate lyase holoenzyme in complex with citrate, coenzyme A and Mg.ADP==
<StructureSection load='6qfb' size='340' side='right'caption='[[6qfb]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qfb]] 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=6QFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QFB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HP:DIHYDROGENPHOSPHATE+ION'>2HP</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6qfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfb OCA], [https://pdbe.org/6qfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qfb RCSB], [https://www.ebi.ac.uk/pdbsum/6qfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfb ProSAT]</span></td></tr>
</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 ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qfb" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATP-citrate synthase 3D structures|ATP-citrate synthase 3D structures]]
*[[Kallikrein 3D structures|Kallikrein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Verschueren K]]
[[Category: Verstraete K]]