6tl3: Difference between revisions
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==Crystal structure of an Estrogen Receptor alpha 8-mer phosphopeptide in complex with 14-3-3sigma stabilized by a Pyrrolidone1 derivative== | |||
<StructureSection load='6tl3' size='340' side='right'caption='[[6tl3]], [[Resolution|resolution]] 2.46Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TL3 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]] 2.455Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=NJW:5-[(2~{S},3~{R})-3-[(~{R})-azanyl(phenyl)methyl]-2-(4-nitrophenyl)-4,5-bis(oxidanylidene)pyrrolidin-1-yl]-2-oxidanyl-benzoic+acid'>NJW</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6tl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tl3 OCA], [https://pdbe.org/6tl3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tl3 RCSB], [https://www.ebi.ac.uk/pdbsum/6tl3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tl3 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein-protein interactions (PPIs) of 14-3-3 proteins are a model system for studying PPI stabilization. The complex natural product Fusicoccin A stabilizes many 14-3-3 PPIs but is not amenable for use in SAR studies, motivating the search for more drug-like chemical matter. However, drug-like 14-3-3 PPI stabilizers enabling such studies have remained elusive. An X-ray crystal structure of a PPI in complex with an extremely low potency stabilizer uncovered an unexpected non-protein interacting, ligand-chelated Mg(2+) leading to the discovery of metal-ion-dependent 14-3-3 PPI stabilization potency. This originates from a novel chelation-controlled bioactive conformation stabilization effect. Metal chelation has been associated with pan-assay interference compounds (PAINS) and frequent hitter behavior, but chelation can evidently also lead to true potency gains and find use as a medicinal chemistry strategy to guide compound optimization. To demonstrate this, we exploited the effect to design the first potent, selective, and drug-like 14-3-3 PPI stabilizers. | |||
Design of Drug-Like Protein-Protein Interaction Stabilizers Guided By Chelation-Controlled Bioactive Conformation Stabilization.,Bosica F, Andrei SA, Neves JF, Brandt P, Gunnarsson A, Landrieu I, Ottmann C, O'Mahony G Chemistry. 2020 Jun 2;26(31):7131-7139. doi: 10.1002/chem.202001608. Epub 2020, May 11. PMID:32255539<ref>PMID:32255539</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6tl3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
Latest revision as of 08:22, 17 October 2024
Crystal structure of an Estrogen Receptor alpha 8-mer phosphopeptide in complex with 14-3-3sigma stabilized by a Pyrrolidone1 derivative
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