5sch
From Proteopedia
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==Structure of liver pyruvate kinase in complex with anthraquinone derivative 100== | ==Structure of liver pyruvate kinase in complex with anthraquinone derivative 100== | ||
| - | <StructureSection load='5sch' size='340' side='right'caption='[[5sch]]' scene=''> | + | <StructureSection load='5sch' size='340' side='right'caption='[[5sch]], [[Resolution|resolution]] 2.09Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SCH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sch]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SCH FirstGlance]. <br> |
| - | </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=5sch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sch OCA], [https://pdbe.org/5sch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sch RCSB], [https://www.ebi.ac.uk/pdbsum/5sch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sch ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=I9C:methyl+N-(3-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-sulfonyl)glycinate'>I9C</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></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=5sch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sch OCA], [https://pdbe.org/5sch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sch RCSB], [https://www.ebi.ac.uk/pdbsum/5sch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sch ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis and is considered a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). In this study, we report the first ADP-competitive PKL inhibitors and identify several starting points for the further optimization of these inhibitors. Modeling and structural biology guided the optimization of a PKL-specific anthraquinone-based compound. A structure-activity relationship study of 47 novel synthetic derivatives revealed PKL inhibitors with half-maximal inhibitory concentration (IC50) values in the 200 nM range. Despite the difficulty involved in studying a binding site as exposed as the ADP site, these derivatives feature expanded structural diversity and chemical spaces that may be used to improve their inhibitory activities against PKL. The obtained results expand the knowledge of the structural requirements for interactions with the ADP-binding site of PKL. | ||
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| + | Anthraquinone derivatives as ADP-competitive inhibitors of liver pyruvate kinase.,Nain-Perez A, Foller Fuchtbauer A, Haversen L, Lulla A, Gao C, Matic J, Monjas L, Rodriguez A, Brear P, Kim W, Hyvonen M, Boren J, Mardinoglu A, Uhlen M, Grotli M Eur J Med Chem. 2022 Mar 8;234:114270. doi: 10.1016/j.ejmech.2022.114270. PMID:35290845<ref>PMID:35290845</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5sch" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Brear P]] | + | [[Category: Pyruvate kinase]] |
| - | [[Category: Foller A]] | + | [[Category: Brear, P]] |
| - | [[Category: Grotli M]] | + | [[Category: Foller, A]] |
| - | [[Category: Hyvonen M]] | + | [[Category: Grotli, M]] |
| - | [[Category: Lulla A]] | + | [[Category: Hyvonen, M]] |
| - | [[Category: Nain-Perez A]] | + | [[Category: Lulla, A]] |
| + | [[Category: Nain-Perez, A]] | ||
| + | [[Category: Active site]] | ||
| + | [[Category: Inhibition]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 10:57, 30 March 2022
Structure of liver pyruvate kinase in complex with anthraquinone derivative 100
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