View source for 4mxd


==1.45 angstronm crystal structure of E.coli 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (MenH)==
<StructureSection load='4mxd' size='340' side='right'caption='[[4mxd]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mxd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MXD 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]] 1.45&#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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4mxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mxd OCA], [https://pdbe.org/4mxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mxd RCSB], [https://www.ebi.ac.uk/pdbsum/4mxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mxd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MENH_ECOLI MENH_ECOLI] Catalyzes a proton abstraction reaction that results in 2,5-elimination of pyruvate from 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) and the formation of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). Is also able to catalyze the hydrolysis of the thioester bond in palmitoyl-CoA in vitro.<ref>PMID:15808744</ref> <ref>PMID:18284213</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to be a specific general base by an open-closed conformational change in the catalysis of 2-succinyl-6-hydroxy-2, 4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of a half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche-conformation to form the functional triad. NMR analysis shows that the inactive, open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couple formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the triad off its nucelophilicity, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis.

Molecular Basis of the General Base Catalysis of an alpha/beta-Hydrolase Catalytic Triad.,Sun Y, Yin S, Feng Y, Li J, Zhou J, Liu C, Zhu G, Guo Z J Biol Chem. 2014 Apr 15. PMID:24737327<ref>PMID:24737327</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4mxd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Feng Y]]
[[Category: Guo Z]]
[[Category: Li J]]
[[Category: Liu C]]
[[Category: Sun Y]]
[[Category: Yin S]]
[[Category: Zhou J]]
[[Category: Zhu G]]