View source for 3nbw


==X-ray structure of ketohexokinase in complex with a pyrazole compound==
<StructureSection load='3nbw' size='340' side='right'caption='[[3nbw]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nbw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NBW 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]] 2.341&#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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TR4:5-AMINO-3-(METHYLSULFANYL)-1-PHENYL-1H-PYRAZOLE-4-CARBONITRILE'>TR4</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=3nbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nbw OCA], [https://pdbe.org/3nbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nbw RCSB], [https://www.ebi.ac.uk/pdbsum/3nbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nbw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:[https://omim.org/entry/229800 229800]. Benign defect of intermediary metabolism.<ref>PMID:19237742</ref> <ref>PMID:7833921</ref> 
== Function ==
[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments to leadlike compounds. Applying electron density of fragments within the protein binding site as defined by X-ray crystallography, one can generate target specific leads without the use of affinity data. Our approach contrasts with most fragment-based drug design methodology where solution activity is a main design guide. Herein we describe the discovery of submicromolar ketohexokinase inhibitors with promising druglike properties.

Electron density guided fragment-based lead discovery of ketohexokinase inhibitors.,Gibbs AC, Abad MC, Zhang X, Tounge BA, Lewandowski FA, Struble GT, Sun W, Sui Z, Kuo LC J Med Chem. 2010 Nov 25;53(22):7979-91. Epub 2010 Oct 29. PMID:21033679<ref>PMID:21033679</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3nbw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ketohexokinase|Ketohexokinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abad MC]]
[[Category: Gibbs AC]]
[[Category: Spurlino JC]]