View source for 6sfh


==CRYSTAL STRUCTURE OF DHQ1 FROM Staphylococcus aureus COVALENTLY MODIFIED BY LIGAND 7==
<StructureSection load='6sfh' size='340' side='right'caption='[[6sfh]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SFH 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]] 1.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L9Z:(1~{S},3~{S},4~{S},5~{R})-3-(aminomethyl)-3,4,5-tris(hydroxyl)cyclohexane-1-carboxylic+acid'>L9Z</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</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=6sfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sfh OCA], [https://pdbe.org/6sfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sfh RCSB], [https://www.ebi.ac.uk/pdbsum/6sfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sfh ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Disabling the bacterial capacity to cause infection is an innovative approach that has attracted significant attention to fight against superbugs. A relevant target for anti-virulence drug discovery is the type I dehydroquinase (DHQ1) enzyme. It was shown that the 2-hydroxyethylammonium derivative 3 has in vitro activity since it causes the covalent modification of the catalytic lysine residue of DHQ1. As this compound does not bear reactive electrophilic centers, how the chemical modification occurs is intriguing. We report here an integrated approach, which involves biochemical studies, X-ray crystallography and computational studies on the reaction path using combined quantum mechanics/molecular mechanics Umbrella Sampling Molecular Dynamics, that evidences that DHQ1 catalyzes its self-immolation by transforming the unreactive 2-hydroxyethylammonium group in 3 into an epoxide that triggers the lysine covalent modification. This finding might open opportunities for the design of lysine-targeted irreversible inhibitors bearing a 2-hydroxyethylammonium moiety as an epoxide proform, which to our knowledge has not been reported previously.

Self-Immolation of a Bacterial Dehydratase Enzyme by its Epoxide Product.,Lence E, Maneiro M, Sanz-Gaitero M, van Raaij MJ, Thompson P, Hawkins AR, Gonzalez-Bello C Chemistry. 2020 Apr 7. doi: 10.1002/chem.202000759. PMID:32259333<ref>PMID:32259333</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 6sfh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dehydroquinase 3D structures|Dehydroquinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Gonzalez-Bello C]]
[[Category: Hawkins AR]]
[[Category: Lence E]]
[[Category: Maneiro M]]
[[Category: Sanz-Gaitero M]]
[[Category: Thompson R]]
[[Category: Van Raaij MJ]]