3ozj

Crystal structure of human retinoic X receptor alpha complexed with bigelovin and coactivator SRC-1Crystal structure of human retinoic X receptor alpha complexed with bigelovin and coactivator SRC-1

Structural highlights 3ozj is a 4 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 2.1Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RXRA_HUMAN Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Publication Abstract from PubMed The nuclear receptor retinoid X receptor (RXR) functions potently in the regulation of homeostasis and cell development, while rexinoids as RXR agonists have proved their therapeutic potential in the treatment of metabolic diseases and cancer. Here, the natural product bigelovin was identified as a selective RXRalpha agonist. Interestingly, this compound could not transactivate RXRalpha:RXRalpha homodimer but could enhance the transactivation of RXRalpha:peroxisome proliferator-activated receptor gamma heterodimer and repress that of RXRalpha:liver X receptor (LXR) alpha heterodimer, while it had no effects on RXRalpha:farnesoid X receptor heterodimer. Considering that the effective role of LXR response element involved transactivation of sterol regulatory element-binding protein-1c mediated by RXRalpha:LXRalpha in triglyceride elevation, such LXR response element repressing by bigelovin has obviously addressed its potency for further research. Moreover, our determined crystal structure of the bigelovin-activated RXRalpha ligand-binding domain with the coactivator human steroid receptor coactivator-1 peptide revealed that bigelovin adopted a distinct binding mode. Compared with the known RXR ligands, bigelovin lacks the acidic moiety in structure, which indicated that the acidic moiety rendered little effects on RXR activation. Our results have thereby provided new insights into the structure-based selective rexinoids design with bigelovin as a potential lead compound. Structure basis of bigelovin as a selective RXR agonist with a distinct binding mode.,Zhang H, Li L, Chen L, Hu L, Jiang H, Shen X J Mol Biol. 2011 Mar 18;407(1):13-20. Epub 2011 Jan 22. PMID:21262235 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retinoid X receptor 3D structures

spinqualitylabelsall models 3ozj, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image