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==Unravelling the B. pseudomallei heptokinase WcbL: from Structure to Drug Discovery.==
<StructureSection load='4usk' size='340' side='right'caption='[[4usk]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4usk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_K96243 Burkholderia pseudomallei K96243]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4USK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4USK 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]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</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=4usk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4usk OCA], [https://pdbe.org/4usk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4usk RCSB], [https://www.ebi.ac.uk/pdbsum/4usk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4usk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H7C745_BURPS H7C745_BURPS] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gram-negative bacteria utilize heptoses as part of their repertoire of extracellular polysaccharide virulence determinants. Disruption of heptose biosynthesis offers an attractive target for novel antimicrobials. A critical step in the synthesis of heptoses is their 1-O phosphorylation, mediated by kinases such as HldE or WcbL. Here, we present the structure of WcbL from Burkholderia pseudomallei. We report that WcbL operates through a sequential ordered Bi-Bi mechanism, loading the heptose first and then ATP. We show that dimeric WcbL binds ATP anti-cooperatively in the absence of heptose, and cooperatively in its presence. Modeling of WcbL suggests that heptose binding causes an elegant switch in the hydrogen-bonding network, facilitating the binding of a second ATP molecule. Finally, we screened a library of drug-like fragments, identifying hits that potently inhibit WcbL. Our results provide a novel mechanism for control of substrate binding and emphasize WcbL as an attractive anti-microbial target for Gram-negative bacteria.

Unraveling the B. pseudomallei Heptokinase WcbL: From Structure to Drug Discovery.,Vivoli M, Isupov MN, Nicholas R, Hill A, Scott AE, Kosma P, Prior JL, Harmer NJ Chem Biol. 2015 Dec 17;22(12):1622-32. doi: 10.1016/j.chembiol.2015.10.015. PMID:26687481<ref>PMID:26687481</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4usk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Burkholderia pseudomallei K96243]]
[[Category: Large Structures]]
[[Category: Harmer NJ]]
[[Category: Hill A]]
[[Category: Isupov MN]]
[[Category: Kosma P]]
[[Category: Nicholas R]]
[[Category: Prior J]]
[[Category: Scott A]]
[[Category: Vivoli M]]