View source for 1m4s


==Biosynthetic thiolase, Cys89 acetylated, unliganded form==
<StructureSection load='1m4s' size='340' side='right'caption='[[1m4s]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1m4s]] 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=1M4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4S 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]] 1.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SCY:S-ACETYL-CYSTEINE'>SCY</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=1m4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4s OCA], [https://pdbe.org/1m4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4s RCSB], [https://www.ebi.ac.uk/pdbsum/1m4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4s 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/m4/1m4s_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1m4s ConSurf].
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== Publication Abstract from PubMed ==
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.

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:12501183<ref>PMID:12501183</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1m4s" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thiolase 3D structures|Thiolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Zoogloea ramigera]]
[[Category: Kursula P]]
[[Category: Lambeir A-M]]
[[Category: Ojala J]]
[[Category: Wierenga RK]]