1x7e

CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH WAY-244CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH WAY-244

Structural highlights 1x7e is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1u3q, 1u3r, 1u3s, 1u9e, 1x76, 1x78, 1x7b, 1x7d, 1x7j, 1x7r Gene: ESR1, NR3A1, ESR (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum 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 the structure-based optimization of a series of estrogen receptor-beta (ERbeta) selective ligands. X-ray cocrystal structures of these ligands complexed to both ERalpha and ERbeta are described. We also discuss how molecular modeling was used to take advantage of subtle differences between the two binding cavities in order to optimize selectivity for ERbeta over ERalpha. Quantum chemical calculations are utilized to gain insight into the mechanism of selectivity enhancement. Despite only two relatively conservative residue substitutions in the ligand binding pocket, the most selective compounds have greater than 100-fold selectivity for ERbeta relative to ERalpha when measured using a competitive radioligand binding assay. Structure-based design of estrogen receptor-beta selective ligands.,Manas ES, Unwalla RJ, Xu ZB, Malamas MS, Miller CP, Harris HA, Hsiao C, Akopian T, Hum WT, Malakian K, Wolfrom S, Bapat A, Bhat RA, Stahl ML, Somers WS, Alvarez JC J Am Chem Soc. 2004 Nov 24;126(46):15106-19. PMID:15548008 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Estrogen receptor

spinqualitylabelsall models 1x7e, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image