3k8x
From Proteopedia
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==Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with tepraloxydim== | ==Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with tepraloxydim== | ||
| - | <StructureSection load='3k8x' size='340' side='right' caption='[[3k8x]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3k8x' size='340' side='right'caption='[[3k8x]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3k8x]] is a 3 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3k8x]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K8X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B89:(5S)-2-[(1E)-N-{[(2E)-3-CHLOROPROP-2-EN-1-YL]OXY}PROPANIMIDOYL]-3-HYDROXY-5-(TETRAHYDRO-2H-PYRAN-4-YL)CYCLOHEX-2-EN-1-ONE'>B89</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B89:(5S)-2-[(1E)-N-{[(2E)-3-CHLOROPROP-2-EN-1-YL]OXY}PROPANIMIDOYL]-3-HYDROXY-5-(TETRAHYDRO-2H-PYRAN-4-YL)CYCLOHEX-2-EN-1-ONE'>B89</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=3k8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k8x OCA], [https://pdbe.org/3k8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k8x RCSB], [https://www.ebi.ac.uk/pdbsum/3k8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k8x ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ACAC_YEAST 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.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k8/3k8x_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k8/3k8x_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3k8x ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3k8x ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and are attractive targets for drug discovery. Haloxyfop and tepraloxydim belong to two distinct classes of commercial herbicides and kill sensitive plants by inhibiting the carboxyltransferase (CT) activity of ACC. Our earlier structural studies showed that haloxyfop is bound near the active site of the CT domain, at the interface of its dimer, and a large conformational change in the dimer interface is required for haloxyfop binding. We report here the crystal structure at 2.3 A resolution of the CT domain of yeast ACC in complex with tepraloxydim. The compound has a different mechanism of inhibiting the CT activity compared to haloxyfop, as well as the mammalian ACC inhibitor CP-640186. Tepraloxydim probes a different region of the dimer interface and requires only small but important conformational changes in the enzyme, in contrast to haloxyfop. The binding mode of tepraloxydim explains the structure-activity relationship of these inhibitors, and provides a molecular basis for their distinct sensitivity to some of the resistance mutations, as compared to haloxyfop. Despite the chemical diversity between haloxyfop and tepraloxydim, the compounds do share two binding interactions to the enzyme, which may be important anchoring points for the development of ACC inhibitors. | ||
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| - | A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim.,Xiang S, Callaghan MM, Watson KG, Tong L Proc Natl Acad Sci U S A. 2009 Nov 19. PMID:19926852<ref>PMID:19926852</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3k8x" style="background-color:#fffaf0;"></div> | ||
==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: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: | + | [[Category: Callaghan MM]] |
| - | [[Category: | + | [[Category: Tong L]] |
| - | [[Category: | + | [[Category: Watson KG]] |
| - | [[Category: | + | [[Category: Xiang S]] |
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Current revision
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with tepraloxydim
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