View source for 6mbf


==GphF Dehydratase 1==
<StructureSection load='6mbf' size='340' side='right'caption='[[6mbf]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mbf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Archangium_violaceum Archangium violaceum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MBF 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]] 1.543&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6mbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mbf OCA], [https://pdbe.org/6mbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mbf RCSB], [https://www.ebi.ac.uk/pdbsum/6mbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mbf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/U6BSB2_9DELT U6BSB2_9DELT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Polyketide synthases (PKS) are a rich source of natural products of varied chemical composition and biological significance. Here, we report the characterization of an atypical dehydratase (DH) domain from the PKS pathway for gephyronic acid, an inhibitor of eukaryotic protein synthesis. Using a library of synthetic substrate mimics, the reaction course, stereospecificity, and tolerance to non-native substrates of GphF DH1 are probed via LC-MS analysis. Taken together, the studies establish GphF DH1 as a dual-function dehydratase/isomerase that installs an odd-to-even double bond and yields a product consistent with the isobutenyl terminus of gephyronic acid. The studies also reveal an unexpected C2 epimerase function in catalytic turnover with the native substrate. A 1.55-A crystal structure of GphF DH1 guided mutagenesis experiments to elucidate the roles of key amino acids in the multistep DH1 catalysis, identifying critical functions for leucine and tyrosine side chains. The mutagenesis results were applied to add a secondary isomerase functionality to a nonisomerizing DH in the first successful gain-of-function engineering of a PKS DH. Our studies of GphF DH1 catalysis highlight the versatility of the DH active site and adaptation for a specific catalytic outcome with a specific substrate.

Molecular Basis for Olefin Rearrangement in the Gephyronic Acid Polyketide Synthase.,Dodge GJ, Ronnow D, Taylor RE, Smith JL ACS Chem Biol. 2018 Sep 12. doi: 10.1021/acschembio.8b00645. PMID:30179448<ref>PMID:30179448</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mbf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Archangium violaceum]]
[[Category: Large Structures]]
[[Category: Dodge GJ]]
[[Category: Smith JL]]