2w8y

RU486 bound to the progesterone receptor in a destabilized agonistic conformation

spinqualitylabelsall models 2w8y, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w8y 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 1.8Å Ligands: 486, EDO, NDR, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRGR_HUMAN The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation. Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Here we describe the 1.95 A structure of the clinically used antiprogestin RU486 (mifepristone) in complex with the progesterone receptor (PR). The structure was obtained by taking a crystal of the PR ligand binding domain containing the agonist norethindrone and soaking it in a solution containing the antagonist RU486 for extended times. Clear ligand exchange could be observed in one copy of the PR ligand binding domain dimer in the crystal. RU486 binds while PR is in an agonistic conformation without displacing helix 12. Although this is probably because of the constraints of the crystal lattice, it demonstrates that helix 12 displacement is not a prerequisite for RU486 binding. Interestingly, B-factor analysis clearly shows that helix 12 becomes more flexible after RU486 binding, suggesting that RU486, being a model antagonist, does not induce one fixed conformation of helix 12 but changes its positional equilibrium. This conclusion is confirmed by comparing the structures of RU486 bound to PR and RU486 bound to the glucocorticoid receptor. The X-ray structure of RU486 bound to the progesterone receptor in a destabilized agonistic conformation.,Raaijmakers HC, Versteegh JE, Uitdehaag JC J Biol Chem. 2009 Jul 17;284(29):19572-9. Epub 2009 Apr 16. PMID:19372222 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Progesterone receptor

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