5wi0: Difference between revisions
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==Crystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one== | |||
<StructureSection load='5wi0' size='340' side='right' caption='[[5wi0]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5wi0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WI0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WI0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AQ1:2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one'>AQ1</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </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=5wi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wi0 OCA], [http://pdbe.org/5wi0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wi0 RCSB], [http://www.ebi.ac.uk/pdbsum/5wi0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wi0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor. | |||
Fragment-based discovery of a potent NAMPT inhibitor.,Korepanova A, Longenecker KL, Pratt SD, Panchal SC, Clark RF, Lake M, Gopalakrishnan SM, Raich D, Sun C, Petros AM Bioorg Med Chem Lett. 2017 Dec 12. pii: S0960-894X(17)31183-6. doi:, 10.1016/j.bmcl.2017.12.023. PMID:29287958<ref>PMID:29287958</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5wi0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Nicotinamide phosphoribosyltransferase]] | |||
[[Category: Korepanova, A V]] | |||
[[Category: Longenecker, K L]] | |||
[[Category: Raich, D]] | |||
[[Category: Inhibitor]] | |||
[[Category: Nampt]] | |||
[[Category: Transferase]] | |||
[[Category: Transferase-transferase inhibitor complex]] | |||
Revision as of 08:28, 10 January 2018
Crystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one
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