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| | ==Crystal structure of the BC domain of ACC2 in complex with soraphen A== | | ==Crystal structure of the BC domain of ACC2 in complex with soraphen A== |
| - | <StructureSection load='3jrx' size='340' side='right' caption='[[3jrx]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3jrx' size='340' side='right'caption='[[3jrx]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3jrx]] is a 1 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=3JRX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JRX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3jrx]] is a 1 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=3JRX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JRX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=S1A:SORAPHEN+A'>S1A</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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hjw|2hjw]], [[3jrw|3jrw]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S1A:SORAPHEN+A'>S1A</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACACB, ACC2, ACCB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3jrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jrx OCA], [https://pdbe.org/3jrx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jrx RCSB], [https://www.ebi.ac.uk/pdbsum/3jrx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jrx ProSAT]</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=3jrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jrx OCA], [http://pdbe.org/3jrx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jrx RCSB], [http://www.ebi.ac.uk/pdbsum/3jrx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jrx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN]] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. | + | [https://www.uniprot.org/uniprot/ACACB_HUMAN ACACB_HUMAN] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Acetyl-CoA carboxylase|Acetyl-CoA carboxylase]] | + | *[[Acetyl-CoA carboxylase 3D structures|Acetyl-CoA carboxylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cho, Y S]] | + | [[Category: Large Structures]] |
| - | [[Category: Heo, Y S]] | + | [[Category: Cho YS]] |
| - | [[Category: Kim, H T]] | + | [[Category: Heo YS]] |
| - | [[Category: Lee, J I]] | + | [[Category: Kim HT]] |
| - | [[Category: Lee, T G]] | + | [[Category: Lee JI]] |
| - | [[Category: Shin, D]] | + | [[Category: Lee TG]] |
| - | [[Category: Alternative splicing]] | + | [[Category: Shin D]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Bc domain]]
| + | |
| - | [[Category: Biotin]]
| + | |
| - | [[Category: Fatty acid biosynthesis]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Lipid synthesis]]
| + | |
| - | [[Category: Manganese]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Multifunctional enzyme]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Soraphen some]]
| + | |
| Structural highlights
Function
ACACB_HUMAN ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes, as they play crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here, we report the crystal structures of the biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK). The phosphorylated Ser222 binds to the putative dimer interface of BC, disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product. This structure shows that the compound binds to the binding site of phosphorylated Ser222, implying that its inhibition mechanism is the same as that of phosphorylation by AMPK.
Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK.,Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS Biochem Biophys Res Commun. 2010 Jan 1;391(1):187-92. Epub 2009 Nov 10. PMID:19900410[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS. Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK. Biochem Biophys Res Commun. 2010 Jan 1;391(1):187-92. Epub 2009 Nov 10. PMID:19900410 doi:10.1016/j.bbrc.2009.11.029
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