4y32: Difference between revisions
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<StructureSection load='4y32' size='340' side='right'caption='[[4y32]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4y32' size='340' side='right'caption='[[4y32]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4y32]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4y32]] 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=4Y32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y32 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=49F:(2S)-2-(2-METHOXYETHYL)PYRROLIDINE'>49F</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=49F:(2S)-2-(2-METHOXYETHYL)PYRROLIDINE'>49F</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4y32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y32 OCA], [https://pdbe.org/4y32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y32 RCSB], [https://www.ebi.ac.uk/pdbsum/4y32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y32 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Microtubule-associated protein|Microtubule-associated protein]] | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] | ||
*[[Tau protein|Tau protein]] | *[[Tau protein 3D structures|Tau protein 3D structures]] | ||
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | ||
== References == | == References == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bartel | [[Category: Bartel M]] | ||
[[Category: Bier | [[Category: Bier D]] | ||
[[Category: Brunsveld | [[Category: Brunsveld L]] | ||
[[Category: Milroy | [[Category: Milroy L]] | ||
[[Category: Ottmann | [[Category: Ottmann C]] | ||
Revision as of 21:04, 26 April 2023
Crystal structure of C-terminal modified Tau peptide-hybrid 109B with 14-3-3sigmaCrystal structure of C-terminal modified Tau peptide-hybrid 109B with 14-3-3sigma
Structural highlights
Function1433S_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. Publication Abstract from PubMedThe discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs. Stabilizer-Guided Inhibition of Protein-Protein Interactions.,Milroy LG, Bartel M, Henen MA, Leysen S, Adriaans JM, Brunsveld L, Landrieu I, Ottmann C Angew Chem Int Ed Engl. 2015 Nov 5. doi: 10.1002/anie.201507976. PMID:26537010[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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