11se: Difference between revisions
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==Covalent stabilizer compound 8 for the interaction between 14-3-3 sigma and Estrogen receptor-alpha peptide== | |||
<StructureSection load='11se' size='340' side='right'caption='[[11se]], [[Resolution|resolution]] 2.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[11se]] is a 4 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=11SE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=11SE 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]] 2.239Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DAD:3-chloro-5-{[(1S)-1-methoxy-1-methyl-3-oxo-1,3-dihydro-2-benzofuran-4-yl]oxy}-4H-1,2,6-thiadiazin-4-one'>A1DAD</scene>, <scene name='pdbligand=A1DAE:3-chloro-5-{[(1R)-1-methoxy-1-methyl-3-oxo-1,3-dihydro-2-benzofuran-4-yl]oxy}-4H-1,2,6-thiadiazin-4-one'>A1DAE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=11se FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=11se OCA], [https://pdbe.org/11se PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=11se RCSB], [https://www.ebi.ac.uk/pdbsum/11se PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=11se ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Selective stabilization of complexes formed by the hub protein 14-3-3 represents an emerging mechanism for the modulation of therapeutically relevant targets. In this letter, we describe a hit-finding campaign designed to identify small molecule stabilizers of the interaction between 14-3-3sigma and the estrogen receptor alpha (ERalpha). Four structurally distinct hits were identified and validated using a combination of biochemical assays and biophysical techniques. Ternary complex crystal structures revealed that all four hit compounds form a covalent bond with Cys38 of 14-3-3sigma via four different electrophilic warheads. Structure-based optimization of the most promising hit compound 9 led to dramatic improvements in stabilization activity and selectivity that exceeded the complex natural product fusicoccin A. | |||
Covalent Stabilizers of the Interaction Between 14-3-3sigma and Estrogen Receptorâalpha.,Jain R, Knapp M, Kochanek SE, Lewis A, McGregor LM, Stojkovic V, Tang J, Tsang T, Yan K, Yifru A, Zhu Q, Fabbiani F, Feng G, Frank AO, Fuller J, Jahnke W, Jansen JM, Jo J, Li M, Lipps J, Lu Y, Mladenovic T, Piechon P, Rogemoser P, Wang F, Yang S, Skepper CK ACS Med Chem Lett. 2026 Aug 17;17(9):2006-2016. doi: , 10.1021/acsmedchemlett.6c00325. eCollection 2026 Sep 10. PMID:42741630<ref>PMID:42741630</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Knapp | <div class="pdbe-citations 11se" style="background-color:#fffaf0;"></div> | ||
[[Category: Tang | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Knapp MS]] | |||
[[Category: Tang JY]] | |||
Latest revision as of 09:56, 30 September 2026
Covalent stabilizer compound 8 for the interaction between 14-3-3 sigma and Estrogen receptor-alpha peptide
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