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| [[Image:1m4t.gif|left|200px]]<br /><applet load="1m4t" size="350" color="white" frame="true" align="right" spinBox="true"
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| caption="1m4t, resolution 1.77Å" />
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| '''Biosynthetic thiolase, Cys89 butyrylated'''<br />
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| ==Overview== | | ==Biosynthetic thiolase, Cys89 butyrylated== |
| Biosynthetic thiolase catalyzes the formation of acetoacetyl-CoA from two molecules of acetyl-CoA. This is a key step in the synthesis of many biological compounds, including steroid hormones and ketone bodies. The thiolase reaction involves two chemically distinct steps; during acyl transfer, an acetyl group is transferred from acetyl-CoA to Cys89, and in the Claisen condensation step, this acetyl group is further transferred to a second molecule of acetyl-CoA, generating acetoacetyl-CoA. Here, new crystallographic data for Zoogloea ramigera biosynthetic thiolase are presented, covering all intermediates of the thiolase catalytic cycle. The high-resolution structures indicate that the acetyl group goes through four conformations while being transferred from acetyl-CoA via the acetylated enzyme to acetoacetyl-CoA. This transfer is catalyzed in a rigid cavity lined by mostly hydrophobic side chains, in addition to the catalytic residues Cys89, His348, and Cys378. The structures highlight the importance of an oxyanion hole formed by a water molecule and His348 in stabilizing the negative charge on the thioester oxygen atom of acetyl-CoA at two different steps of the reaction cycle. Another oxyanion hole, composed of the main chain nitrogen atoms of Cys89 and Gly380, complements a negative charge of the thioester oxygen anion of the acetylated intermediate, stabilizing the tetrahedral transition state of the Claisen condensation step. The reactivity of the active site may be modulated by hydrogen bonding networks extending from the active site toward the back of the molecule.
| | <StructureSection load='1m4t' size='340' side='right'caption='[[1m4t]], [[Resolution|resolution]] 1.77Å' scene=''> |
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1m4t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Zoogloea_ramigera Zoogloea ramigera]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4T 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]] 1.77Å</td></tr> |
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CY4:S-BUTYRYL-CYSTEIN'>CY4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1m4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4t OCA], [https://pdbe.org/1m4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4t RCSB], [https://www.ebi.ac.uk/pdbsum/1m4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4t ProSAT]</span></td></tr> |
| | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/THIL_SHIZO THIL_SHIZO] |
| | == 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/m4/1m4t_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=1m4t ConSurf]. |
| | <div style="clear:both"></div> |
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| ==About this Structure== | | ==See Also== |
| 1M4T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zoogloea_ramigera Zoogloea ramigera] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetyl-CoA_C-acetyltransferase Acetyl-CoA C-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.9 2.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4T OCA].
| | *[[Thiolase 3D structures|Thiolase 3D structures]] |
| | | __TOC__ |
| ==Reference==
| | </StructureSection> |
| The catalytic cycle of biosynthetic thiolase: a conformational journey of an acetyl group through four binding modes and two oxyanion holes., Kursula P, Ojala J, Lambeir AM, Wierenga RK, Biochemistry. 2002 Dec 31;41(52):15543-56. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12501183 12501183]
| | [[Category: Large Structures]] |
| [[Category: Acetyl-CoA C-acetyltransferase]]
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| [[Category: Single protein]] | |
| [[Category: Zoogloea ramigera]] | | [[Category: Zoogloea ramigera]] |
| [[Category: Kursula, P.]] | | [[Category: Kursula P]] |
| [[Category: Lambeir, A M.]] | | [[Category: Lambeir A-M]] |
| [[Category: Ojala, J.]] | | [[Category: Ojala J]] |
| [[Category: Wierenga, R K.]] | | [[Category: Wierenga RK]] |
| [[Category: GOL]]
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| [[Category: SO4]]
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| [[Category: butyrylated intermediate]]
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| [[Category: thiolase fold]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:26 2008''
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