View source for 5ajz


==Human PFKFB3 in complex with an indole inhibitor 5==
<StructureSection load='5ajz' size='340' side='right'caption='[[5ajz]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ajz]] is a 1 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=5AJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AJZ 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F6P:FRUCTOSE-6-PHOSPHATE'>F6P</scene>, <scene name='pdbligand=MJP:2-AZANYL-N-[4-[(3-CYANO-1H-INDOL-5-YL)OXY]PHENYL]ETHANAMIDE'>MJP</scene>, <scene name='pdbligand=PHS:PHOSPHONIC+ACID'>PHS</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5ajz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ajz OCA], [https://pdbe.org/5ajz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ajz RCSB], [https://www.ebi.ac.uk/pdbsum/5ajz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ajz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F263_HUMAN F263_HUMAN] Synthesis and degradation of fructose 2,6-bisphosphate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.

Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3.,Boyd S, Brookfield JL, Critchlow SE, Cumming IA, Curtis NJ, Debreczeni J, Degorce SL, Donald C, Evans NJ, Groombridge S, Hopcroft P, Jones NP, Kettle JG, Lamont S, Lewis HJ, MacFaull P, McLoughlin SB, Rigoreau LJ, Smith JM, St-Gallay S, Stock JK, Turnbull AP, Wheatley ER, Winter J, Wingfield J J Med Chem. 2015 Apr 13. PMID:25849762<ref>PMID:25849762</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ajz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boyd S]]
[[Category: Brookfield JL]]
[[Category: Critchlow SE]]
[[Category: Cumming IA]]
[[Category: Curtis NJ]]
[[Category: Debreczeni JE]]
[[Category: Degorce SL]]
[[Category: Donald C]]
[[Category: Evans NJ]]
[[Category: Groombridge S]]
[[Category: Hopcroft P]]
[[Category: Jones NP]]
[[Category: Kettle JG]]
[[Category: Lamont S]]
[[Category: Lewis HJ]]
[[Category: MacFaull P]]
[[Category: McLoughlin SB]]
[[Category: Rigoreau LJM]]
[[Category: Smith JM]]
[[Category: St-Gallay S]]
[[Category: Stock JK]]
[[Category: Wheatley ER]]
[[Category: Wingfield J]]
[[Category: Winter J]]