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5trc

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Revision as of 19:16, 15 November 2017

Crystal structure of phosphorylated AC3-AC5 domains of yeast acetyl-CoA carboxylase

Structural highlights

5trc is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 (Baker's yeast)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACAC_YEAST] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and attractive targets for drug discovery. Eukaryotic acetyl-CoA carboxylases are 250 kDa single-chain, multi-domain enzymes and function as dimers and higher oligomers. Their catalytic activity is tightly regulated by phosphorylation and other means. Here we show that yeast ACC is directly phosphorylated by the protein kinase SNF1 at residue Ser1157, which potently inhibits the enzyme. Crystal structure of three ACC central domains (AC3-AC5) shows that the phosphorylated Ser1157 is recognized by Arg1173, Arg1260, Tyr1113 and Ser1159. The R1173A/R1260A double mutant is insensitive to SNF1, confirming that this binding site is crucial for regulation. Electron microscopic studies reveal dramatic conformational changes in the holoenzyme upon phosphorylation, likely owing to the dissociation of the biotin carboxylase domain dimer. The observations support a unified molecular mechanism for the regulation of ACC by phosphorylation as well as by the natural product soraphen A, a potent inhibitor of eukaryotic ACC. These molecular insights enhance our understanding of acetyl-CoA carboxylase regulation and provide a basis for drug discovery.

A unified molecular mechanism for the regulation of acetyl-CoA carboxylase by phosphorylation.,Wei J, Zhang Y, Yu TY, Sadre-Bazzaz K, Rudolph MJ, Amodeo GA, Symington LS, Walz T, Tong L Cell Discov. 2016 Nov 29;2:16044. eCollection 2016. PMID:27990296^[6]

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

References

↑ Mishina M, Roggenkamp R, Schweizer E. Yeast mutants defective in acetyl-coenzyme A carboxylase and biotin: apocarboxylase ligase. Eur J Biochem. 1980 Oct;111(1):79-87. PMID:6108218
↑ Roggenkamp R, Numa S, Schweizer E. Fatty acid-requiring mutant of Saccharomyces cerevisiae defective in acetyl-CoA carboxylase. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1814-7. PMID:6103540
↑ Schneiter R, Hitomi M, Ivessa AS, Fasch EV, Kohlwein SD, Tartakoff AM. A yeast acetyl coenzyme A carboxylase mutant links very-long-chain fatty acid synthesis to the structure and function of the nuclear membrane-pore complex. Mol Cell Biol. 1996 Dec;16(12):7161-72. PMID:8943372
↑ Schneiter R, Guerra CE, Lampl M, Tatzer V, Zellnig G, Klein HL, Kohlwein SD. A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p. Mol Cell Biol. 2000 May;20(9):2984-95. PMID:10757783
↑ Gao H, Sumanaweera N, Bailer SM, Stochaj U. Nuclear accumulation of the small GTPase Gsp1p depends on nucleoporins Nup133p, Rat2p/Nup120p, Nup85p, Nic96p, and the acetyl-CoA carboxylase Acc1p. J Biol Chem. 2003 Jul 11;278(28):25331-40. Epub 2003 May 1. PMID:12730220 doi:http://dx.doi.org/10.1074/jbc.M301607200
↑ Wei J, Zhang Y, Yu TY, Sadre-Bazzaz K, Rudolph MJ, Amodeo GA, Symington LS, Walz T, Tong L. A unified molecular mechanism for the regulation of acetyl-CoA carboxylase by phosphorylation. Cell Discov. 2016 Nov 29;2:16044. eCollection 2016. PMID:27990296 doi:http://dx.doi.org/10.1038/celldisc.2016.44

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/5trc"

@@ Line 3: / Line 3: @@
 <StructureSection load='5trc' size='340' side='right' caption='[[5trc]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5trc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TRC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5trc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TRC FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=5trc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5trc OCA], [http://pdbe.org/5trc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5trc RCSB], [http://www.ebi.ac.uk/pdbsum/5trc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5trc ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Baker's yeast]]
 [[Category: Tong, L]]
 [[Category: Wei, J]]

5trc

From Proteopedia

Revision as of 19:16, 15 November 2017

Crystal structure of phosphorylated AC3-AC5 domains of yeast acetyl-CoA carboxylase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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