1t74 | pdb_00001t74

Crystal structure of the androgen receptor ligand binding domain in complex with a WxxLF motif

spinqualitylabelsall models 1t74, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1t74 is a 2 chain structure with sequence from Chimpansee troglodytes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DHT, EDO, SO4 Related: 1t73, 1t76, 1t79, 1t7f, 1t7m, 1t7r, 1t7t Gene: AR, NR3C4 (Chimpansee troglodytes) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [ANDR_PANTR] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2.Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (By similarity). 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 Prostate cancer is a leading killer of men in the industrialized world. Underlying this disease is the aberrant action of the androgen receptor (AR). AR is distinguished from other nuclear receptors in that after hormone binding, it preferentially responds to a specialized set of coactivators bearing aromatic-rich motifs, while responding poorly to coactivators bearing the leucine-rich "NR box" motifs favored by other nuclear receptors. Under normal conditions, interactions with these AR-specific coactivators through aromatic-rich motifs underlie targeted gene transcription. However, during prostate cancer, abnormal association with such coactivators, as well as with coactivators containing canonical leucine-rich motifs, promotes disease progression. To understand the paradox of this unusual selectivity, we have derived a complete set of peptide motifs that interact with AR using phage display. Binding affinities were measured for a selected set of these peptides and their interactions with AR determined by X-ray crystallography. Structures of AR in complex with FxxLF, LxxLL, FxxLW, WxxLF, WxxVW, FxxFF, and FxxYF motifs reveal a changing surface of the AR coactivator binding interface that permits accommodation of both AR-specific aromatic-rich motifs and canonical leucine-rich motifs. Induced fit provides perfect mating of the motifs representing the known family of AR coactivators and suggests a framework for the design of AR coactivator antagonists. Recognition and accommodation at the androgen receptor coactivator binding interface.,Hur E, Pfaff SJ, Payne ES, Gron H, Buehrer BM, Fletterick RJ PLoS Biol. 2004 Sep;2(9):E274. Epub 2004 Aug 24. PMID:15328534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Androgen receptor

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