View source for 7pco


==BurG E232Q mutant (holo) in complex with 2R,3R-2,3-dihydroxy-6-methyl-heptanoate (12): Biosynthesis of cyclopropanol rings in bacterial toxins==
<StructureSection load='7pco' size='340' side='right'caption='[[7pco]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pco]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_thailandensis_E264 Burkholderia thailandensis E264]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PCO 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7FI:(2R,3R)-6-methyl-2,3-bis(oxidanyl)heptanoic+acid'>7FI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=7pco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pco OCA], [https://pdbe.org/7pco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pco RCSB], [https://www.ebi.ac.uk/pdbsum/7pco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pco ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q2T3G7_BURTA Q2T3G7_BURTA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacteria of the Burkholderia pseudomallei (BP) group pose a global health threat, causing the infectious diseases melioidosis, a common cause of pneumonia and sepsis, and glanders, a contagious zoonosis. A trait of BP bacteria is a conserved gene cluster coding for the biosynthesis of polyketides (malleicyprols) with a reactive cyclopropanol unit that is critical for virulence. Enzymes building this warhead represent ideal targets for antivirulence strategies but the biochemical basis of cyclopropanol formation is unknown. Here we describe the formation of the malleicyprol warhead. We show that BurG, an unusual NAD(+)-dependent member of the ketol-acid reductoisomerase family, constructs the strained cyclopropanol ring. Biochemical assays and a suite of eight crystal structures of native and mutated BurG with bound analogues and inhibitors provide snapshots of each step of the complex reaction mechanism, involving a concealed oxidoreduction and a C-S bond cleavage. Our findings illustrate a remarkable case of neofunctionalisation, where a biocatalyst from central metabolism has been evolutionarily repurposed for warhead production in pathogens.

Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead.,Trottmann F, Ishida K, Ishida-Ito M, Kries H, Groll M, Hertweck C Nat Chem. 2022 Aug;14(8):884-890. doi: 10.1038/s41557-022-01005-z. Epub 2022 Jul , 29. PMID:35906404<ref>PMID:35906404</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pco" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ketol-acid reductoisomerase 3D structures|Ketol-acid reductoisomerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Burkholderia thailandensis E264]]
[[Category: Large Structures]]
[[Category: Groll M]]
[[Category: Hertweck C]]
[[Category: Ishida K]]
[[Category: Ishida M]]
[[Category: Kries H]]
[[Category: Trottmann F]]