8a9g: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 8a9g is ~~ON HOLD until Paper~~ Publication

==Binary complex of 14-3-3 zeta Glucocorticoid Receptor (GR) pT524 peptide stabilised by (R)-para chloropyrrolidone1==

== Structural highlights ==

<table><tr><td colspan='2'>[[8a9g]] 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=8A9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A9G FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QJK:5-[(2~{R})-3-(4-chlorophenyl)carbonyl-2-(4-nitrophenyl)-4-oxidanyl-5-oxidanylidene-2~{H}-pyrrol-1-yl]-2-oxidanyl-benzoic+acid'>QJK</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=8a9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a9g OCA], [https://pdbe.org/8a9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a9g RCSB], [https://www.ebi.ac.uk/pdbsum/8a9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a9g ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>

== 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.

~~Authors~~:

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<ref>PMID:36484727</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Edman K]]

[[Category: Munier CC]]

[[Category: Ottmann C]]

[[Category: Perry MWD]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8a9g is ON HOLD  until Paper Publication
+==Binary complex of 14-3-3 zeta Glucocorticoid Receptor (GR) pT524 peptide stabilised by (R)-para chloropyrrolidone1==
+<StructureSection load='8a9g' size='340' side='right'caption='[[8a9g]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8a9g]] 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=8A9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A9G FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QJK:5-[(2~{R})-3-(4-chlorophenyl)carbonyl-2-(4-nitrophenyl)-4-oxidanyl-5-oxidanylidene-2~{H}-pyrrol-1-yl]-2-oxidanyl-benzoic+acid'>QJK</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=8a9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a9g OCA], [https://pdbe.org/8a9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a9g RCSB], [https://www.ebi.ac.uk/pdbsum/8a9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a9g ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:36484727</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8a9g" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Edman K]]
+[[Category: Munier CC]]
+[[Category: Ottmann C]]
+[[Category: Perry MWD]]