1w96
From Proteopedia
(Difference between revisions)
| (8 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:1w96.png|left|200px]] | ||
| - | + | ==Crystal Structure of Biotin Carboxylase Domain of Acetyl-coenzyme A Carboxylase from Saccharomyces cerevisiae in Complex with Soraphen A== | |
| + | <StructureSection load='1w96' size='340' side='right'caption='[[1w96]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1w96]] 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=1W96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W96 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w96 OCA], [https://pdbe.org/1w96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w96 RCSB], [https://www.ebi.ac.uk/pdbsum/1w96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w96 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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 == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w9/1w96_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=1w96 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism. Soraphen A, a macrocyclic polyketide natural product, is a nanomolar inhibitor against the biotin carboxylase (BC) domain of human, yeast, and other eukaryotic ACCs. Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A. Soraphen has extensive interactions with an allosteric site, about 25 A from the active site. The specificity of soraphen is explained by large structural differences between the eukaryotic and prokaryotic BC in its binding site, confirmed by our studies on the effects of single-site mutations in this binding site. Unexpectedly, our structures suggest that soraphen may bind in the BC dimer interface and inhibit the BC activity by disrupting the oligomerization of this domain. Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes. | ||
| - | + | A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product.,Shen Y, Volrath SL, Weatherly SC, Elich TD, Tong L Mol Cell. 2004 Dec 22;16(6):881-91. PMID:15610732<ref>PMID:15610732</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1w96" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[ | + | *[[Acetyl-CoA carboxylase 3D structures|Acetyl-CoA carboxylase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Large Structures]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| - | [[Category: Elich | + | [[Category: Elich TD]] |
| - | [[Category: Shen | + | [[Category: Shen Y]] |
| - | [[Category: Tong | + | [[Category: Tong L]] |
| - | [[Category: Volrath | + | [[Category: Volrath SL]] |
| - | [[Category: Weatherly | + | [[Category: Weatherly SC]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of Biotin Carboxylase Domain of Acetyl-coenzyme A Carboxylase from Saccharomyces cerevisiae in Complex with Soraphen A
| |||||||||||
