8byg: Difference between revisions
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New page: '''Unreleased structure''' The entry 8byg is ON HOLD until sometime in the future Authors: Visser, E.J., Sijbesma, E., Ottmann, C. Description: fragment-linked stabilizer for ERa -14-3... |
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==fragment-linked stabilizer for ERa - 14-3-3 interaction (1047648)== | |||
<StructureSection load='8byg' size='340' side='right'caption='[[8byg]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8byg]] is a 2 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=8BYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BYG 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]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S6O:~{N}-[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)-methyl-amino]ethyl]-2-(4-chloranylphenoxy)-~{N},2-dimethyl-propanamide'>S6O</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=8byg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8byg OCA], [https://pdbe.org/8byg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8byg RCSB], [https://www.ebi.ac.uk/pdbsum/8byg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8byg ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small-molecule stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. However, the systematic discovery of PPI stabilizers remains a largely unmet challenge. Herein we report a fragment-linking approach targeting the interface of 14-3-3 and a peptide derived from the estrogen receptor alpha (ERalpha) protein. Two classes of fragments-a covalent and a noncovalent fragment-were co-crystallized and subsequently linked, resulting in a noncovalent hybrid molecule in which the original fragment interactions were largely conserved. Supported by 20 crystal structures, this initial hybrid molecule was further optimized, resulting in selective, 25-fold stabilization of the 14-3-3/ERalpha interaction. The high-resolution structures of both the single fragments, their co-crystal structures and those of the linked fragments document a feasible strategy to develop orthosteric PPI stabilizers by linking to an initial tethered fragment. | |||
From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking.,Visser EJ, Jaishankar P, Sijbesma E, Pennings MAM, Vandenboorn EMF, Guillory X, Neitz RJ, Morrow J, Dutta S, Renslo AR, Brunsveld L, Arkin MR, Ottmann C Angew Chem Int Ed Engl. 2023 Sep 11;62(37):e202308004. doi: , 10.1002/anie.202308004. Epub 2023 Aug 1. PMID:37455289<ref>PMID:37455289</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8byg" style="background-color:#fffaf0;"></div> | ||
[[Category: Ottmann | == References == | ||
[[Category: Visser | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ottmann C]] | |||
[[Category: Sijbesma E]] | |||
[[Category: Visser EJ]] | |||
