8byg
From Proteopedia
(Difference between revisions)
(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...) |
|||
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==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: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ottmann C]] | ||
| + | [[Category: Sijbesma E]] | ||
| + | [[Category: Visser EJ]] | ||
Current revision
fragment-linked stabilizer for ERa - 14-3-3 interaction (1047648)
| |||||||||||
