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6uv5

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Revision as of 06:55, 11 April 2020

Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate

6uv5, resolution 3.40Å

Structural highlights

6uv5 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	ACLY (HUMAN)
Activity:	ATP citrate synthase, with EC number 2.3.3.8
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013 Aug 22;51(4):506-18. doi: 10.1016/j.molcel.2013.07.002. Epub 2013 , Aug 8. PMID:23932781 doi:http://dx.doi.org/10.1016/j.molcel.2013.07.002
↑ Wei X, Schultz K, Bazilevsky GA, Vogt A, Marmorstein R. Molecular basis for acetyl-CoA production by ATP-citrate lyase. Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0351-6. doi:, 10.1038/s41594-019-0351-6. PMID:31873304 doi:http://dx.doi.org/10.1038/s41594-019-0351-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6uv5"

@@ Line 3: / Line 3: @@
 <SX load='6uv5' size='340' side='right' viewer='molstar' caption='[[6uv5]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6uv5]] is a 4 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=6UV5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UV5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6uv5]] is a 4 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=6UV5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UV5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></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 ([http://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'>[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='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=6uv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uv5 OCA], [http://pdbe.org/6uv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uv5 RCSB], [http://www.ebi.ac.uk/pdbsum/6uv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uv5 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6uv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uv5 OCA], [http://pdbe.org/6uv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uv5 RCSB], [http://www.ebi.ac.uk/pdbsum/6uv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uv5 ProSAT]</span></td></tr>
 </table>
 == Function ==

6uv5

From Proteopedia

Revision as of 06:55, 11 April 2020

Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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