1x7r | pdb_00001x7r

CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH GENISTEIN

spinqualitylabelsall models 1x7r, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1x7r is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GEN Related: 1u3q, 1u3r, 1u3s, 1u9e, 1x76, 1x78, 1x7b, 1x7j Gene: ESR1, NR3A1, ESR (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1. 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 We present X-ray crystallographic and molecular modeling studies of estrogen receptors-alpha and -beta complexed with the estrogen receptor-beta-selective phytoestrogen genistein, and coactivator-derived NR box peptides containing an LXXLL motif. We demonstrate that the ligand binding mode is essentially identical when genistein is bound to both isoforms, despite the considerably weaker affinity of this ligand for estrogen receptor-alpha. In addition, we examine subtle differences between binding site residues, providing an explanation for why genistein is modestly selective for the beta isoform. To this end, we also present the results of quantum chemical studies and thermodynamic arguments that yield insight to the nature of the interactions leading to estrogen receptor-beta selectivity. The importance of our analysis to structure-based drug design is discussed. Understanding the selectivity of genistein for human estrogen receptor-beta using X-ray crystallography and computational methods.,Manas ES, Xu ZB, Unwalla RJ, Somers WS Structure. 2004 Dec;12(12):2197-207. PMID:15576033 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Estrogen receptor 3D structures User:Luca Toldo

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