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X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. 2008

Keith Biggadike, and Randy K Bledsoe, and Anne M Hassell, and Barrie E Kirk, and Iain M McLay, and Lisa M Shewchuk, and Eugene L Stewart
kb0903@gsk.com

An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17 alpha furoate ester to occupy more fully the lipophilic 17 alpha pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000730 Androstadienes Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D051958 Nuclear Receptor Coactivator 2 A transcription factor that partners with ligand bound GLUCOCORTICOID RECEPTORS and ESTROGEN RECEPTORS to stimulate GENETIC TRANSCRIPTION. It plays an important role in FERTILITY as well as in METABOLISM of LIPIDS. Glucocorticoid Receptor-Interacting Protein 1,Steroid Receptor Coactivator SRC2,Steroid Receptor Coactivator-2,Transcription Intermediary Factor 2,Glucocorticoid Receptor Interacting Protein 1,Steroid Receptor Coactivator 2
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

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