6ui9: Difference between revisions

Revision as of 10:08, 7 July 2021

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

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Structural highlights

6ui9 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:	ACO, OAA
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:https://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:https://dx.doi.org/10.1038/s41594-019-0351-6

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1016/j.molcel.2013.07.002

[2] 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:https://dx.doi.org/10.1038/s41594-019-0351-6

[1]

[2]

@@ Line 3: / Line 3: @@
 <SX load='6ui9' size='340' side='right' viewer='molstar' caption='[[6ui9]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ui9]] 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=6UI9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UI9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ui9]] 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=6UI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UI9 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>
-<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'>[https://proteopedia.org/fgij/fg.htm?mol=6ui9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ui9 OCA], [https://pdbe.org/6ui9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ui9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ui9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ui9 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=6ui9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ui9 OCA], [http://pdbe.org/6ui9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ui9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ui9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ui9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==
@@ Line 19: / Line 18: @@
 </div>
 <div class="pdbe-citations 6ui9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[ATP-citrate synthase 3D structures|ATP-citrate synthase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </SX>
-[[Category: ATP citrate synthase]]
 [[Category: Human]]
 [[Category: Large Structures]]

6ui9: Difference between revisions

Revision as of 10:08, 7 July 2021

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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