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==X-ray structure of ketohexokinase complexed with an indazole compound== | |||
<StructureSection load='3nc9' size='340' side='right' caption='[[3nc9]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3nc9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NC9 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TR3:N-[3-(METHYLSULFANYL)-1-PHENYL-1H-INDAZOL-6-YL]PIPERIDINE-4-CARBOXAMIDE'>TR3</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nbv|3nbv]], [[3nbw|3nbw]], [[3nc2|3nc2]], [[3nca|3nca]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KHK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketohexokinase Ketohexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.3 2.7.1.3] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nc9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nc9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nc9 PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN]] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:[http://omim.org/entry/229800 229800]]. Benign defect of intermediary metabolism.<ref>PMID:19237742</ref> <ref>PMID:7833921</ref> | |||
== Function == | |||
== | <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> | |||
==See Also== | ==See Also== | ||
*[[Ketohexokinase|Ketohexokinase]] | *[[Ketohexokinase|Ketohexokinase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Ketohexokinase]] | [[Category: Ketohexokinase]] | ||
[[Category: Abad, M C | [[Category: Abad, M C]] | ||
[[Category: Gibbs, A C | [[Category: Gibbs, A C]] | ||
[[Category: Spurlino, J C | [[Category: Spurlino, J C]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 20:25, 18 December 2014
X-ray structure of ketohexokinase complexed with an indazole compoundX-ray structure of ketohexokinase complexed with an indazole compound
Structural highlights
Disease[KHK_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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