7pwt

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

spinqualitylabelsall models 7pwt, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pwt 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 2.312Å Ligands: MG, PJN, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 22;65(24):16818-16828. doi: 10.1021/acs.jmedchem.2c01635. , Epub 2022 Dec 9. PMID:36484727 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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