1w2x: Difference between revisions

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-[[Image:1w2x.jpg|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1w2x", creates the "Structure Box" on the page.
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-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-{{STRUCTURE_1w2x|  PDB=1w2x  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF THE CARBOXYLTRANSFERASE DOMAIN OF ACETYL-COENZYME A CARBOXYLASE IN COMPLEX WITH CP-640186'''
+==Crystal structure of the carboxyltransferase domain of acetyl- coenzyme A carboxylase in complex with CP-640186==
+<StructureSection load='1w2x' size='340' side='right'caption='[[1w2x]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1w2x]] 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=1W2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W2X 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]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RCP:(3R)-1-(9-ANTHRYLCARBONYL)-3-(MORPHOLIN-4-YLCARBONYL)-1,4-BIPIPERIDINE'>RCP</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=1w2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w2x OCA], [https://pdbe.org/1w2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w2x RCSB], [https://www.ebi.ac.uk/pdbsum/1w2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w2x 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/w2/1w2x_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=1w2x ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Acetyl-coenzyme A carboxylases (ACCs) are important targets for the development of therapeutic agents against obesity, diabetes, and other diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of these enzymes. Here we report the crystal structure of the yeast CT domain in complex with CP-640186. The inhibitor is bound in the active site at the interface of a dimer of the CT domain. CP-640186 has tight interactions with the putative biotin binding site in the CT domain and demonstrates a distinct mode of inhibiting the CT activity as compared to the herbicides that inhibit plant ACCs. The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT.
-==Overview==
+Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186.,Zhang H, Tweel B, Li J, Tong L Structure. 2004 Sep;12(9):1683-91. PMID:15341732<ref>PMID:15341732</ref>
-Acetyl-coenzyme A carboxylases (ACCs) are important targets for the development of therapeutic agents against obesity, diabetes, and other diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of these enzymes. Here we report the crystal structure of the yeast CT domain in complex with CP-640186. The inhibitor is bound in the active site at the interface of a dimer of the CT domain. CP-640186 has tight interactions with the putative biotin binding site in the CT domain and demonstrates a distinct mode of inhibiting the CT activity as compared to the herbicides that inhibit plant ACCs. The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-W2X is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W2X OCA].
+</div>
+<div class="pdbe-citations 1w2x" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186., Zhang H, Tweel B, Li J, Tong L, Structure. 2004 Sep;12(9):1683-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15341732 15341732]
+*[[Acetyl-CoA carboxylase 3D structures|Acetyl-CoA carboxylase 3D structures]]
-[[Category: Acetyl-CoA carboxylase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Single protein]]
+[[Category: Li J]]
-[[Category: Li, J.]]
+[[Category: Tong L]]
-[[Category: Tong, L.]]
+[[Category: Tweel B]]
-[[Category: Tweel, B.]]
+[[Category: Zhang H]]
-[[Category: Zhang, H.]]
-[[Category: Acc]]
-[[Category: Acetyl-coa carboxylase]]
-[[Category: Carboxyltransferase]]
-[[Category: Cp-640186]]
-[[Category: Crystal structure]]
-[[Category: Ct]]
-[[Category: Inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 13:04:46 2008''