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==X-ray Structure of Ketohexokinase in complex with AMP-PNP and fructose== | |||
<StructureSection load='3nbv' size='340' side='right'caption='[[3nbv]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3nbv]] 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=3NBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NBV 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</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=3nbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nbv OCA], [https://pdbe.org/3nbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nbv RCSB], [https://www.ebi.ac.uk/pdbsum/3nbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nbv 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3nbv" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Ketohexokinase|Ketohexokinase]] | *[[Ketohexokinase|Ketohexokinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Abad | [[Category: Abad MC]] | ||
[[Category: Gibbs | [[Category: Gibbs AC]] | ||
Latest revision as of 12:12, 6 September 2023
X-ray Structure of Ketohexokinase in complex with AMP-PNP and fructoseX-ray Structure of Ketohexokinase in complex with AMP-PNP and fructose
Structural highlights
DiseaseKHK_HUMAN Defects in KHK are the cause of fructosuria (FRUCT) [MIM:229800. Benign defect of intermediary metabolism.[1] [2] FunctionPublication Abstract from PubMedA 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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