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7pwz

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Revision as of 13:10, 1 February 2024

Crystal structure of 14-3-3 sigma in complex with a C-terminal Estrogen Receptoralpha phosphopeptide, stabilised by Pyrrolidone1 derivative 228

Structural highlights

7pwz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Publication Abstract from PubMed

The ubiquitously expressed glucocorticoid receptor (GR) is a nuclear receptor that controls a broad range of biological processes and is activated by steroidal glucocorticoids such as hydrocortisone or dexamethasone. Glucocorticoids are used to treat a wide variety of conditions, from inflammation to cancer but suffer from a range of side effects that motivate the search for safer GR modulators. GR is also regulated outside the steroid-binding site through protein-protein interactions (PPIs) with 14-3-3 adapter proteins. Manipulation of these PPIs will provide insights into noncanonical GR signaling as well as a new level of control over GR activity. We report the first molecular glues that selectively stabilize the 14-3-3/GR PPI using the related nuclear receptor estrogen receptor alpha (ERalpha) as a selectivity target to drive design. These 14-3-3/GR PPI stabilizers can be used to dissect noncanonical GR signaling and enable the development of novel atypical GR modulators.

Designing Selective Drug-like Molecular Glues for the Glucocorticoid Receptor/14-3-3 Protein-Protein Interaction.,Pallesen JS, Munier CC, Bosica F, Andrei SA, Edman K, Gunnarsson A, La Sala G, Putra OD, Srdanovic S, Wilson AJ, Wissler L, Ottmann C, Perry MWD, O'Mahony G J Med Chem. 2022 Dec 9. doi: 10.1021/acs.jmedchem.2c01635. PMID:36484727^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pallesen JS, Munier CC, Bosica F, Andrei SA, Edman K, Gunnarsson A, La Sala G, Putra OD, Srdanovic S, Wilson AJ, Wissler L, Ottmann C, Perry MWD, O'Mahony G. Designing Selective Drug-like Molecular Glues for the Glucocorticoid Receptor/14-3-3 Protein-Protein Interaction. J Med Chem. 2022 Dec 9. doi: 10.1021/acs.jmedchem.2c01635. PMID:36484727 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c01635

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7pwz"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7pwz]] 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=7PWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CQ:2-oxidanyl-5-[(2~{R})-4-oxidanyl-5-oxidanylidene-2-(1-oxidanylidene-3~{H}-2-benzofuran-5-yl)-3-(phenylcarbonyl)-2~{H}-pyrrol-1-yl]benzoic+acid'>8CQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CQ:2-oxidanyl-5-[(2~{R})-4-oxidanyl-5-oxidanylidene-2-(1-oxidanylidene-3~{H}-2-benzofuran-5-yl)-3-(phenylcarbonyl)-2~{H}-pyrrol-1-yl]benzoic+acid'>8CQ</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=7pwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwz OCA], [https://pdbe.org/7pwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwz RCSB], [https://www.ebi.ac.uk/pdbsum/7pwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwz ProSAT]</span></td></tr>
 </table>

7pwz

From Proteopedia

Revision as of 13:10, 1 February 2024

Crystal structure of 14-3-3 sigma in complex with a C-terminal Estrogen Receptoralpha phosphopeptide, stabilised by Pyrrolidone1 derivative 228

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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