3v49 | pdb_00003v49

Structure of ar lbd with activator peptide and sarm inhibitor 1

spinqualitylabelsall models 3v49, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3v49 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: PK0, SO4 Related: 2ama, 2z4j, 3v4a Gene: AR, DHTR, NR3C4 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [ANDR_HUMAN] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:300068]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. [:] [:] Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:313200]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:312300]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. Function [ANDR_HUMAN] 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. Publication Abstract from PubMed A novel selective androgen receptor modulator (SARM) scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-trifluorome thylbenzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A50 = 0.5 mg/kg vs 70 mg/kg). The binding mode of two compounds including (+)-11b within the AR ligand binding domain has been studied by co-crystallization experiments using a coactivator-like peptide. Both compounds bound to the same site and the overall structure of the AR was very similar. Discovery of Diarylhydantoins as New Selective Androgen Receptor Modulators (SARMs).,Nique F, Hebbe S, Peixoto C, Annoot D, Lefrancois JM, Duval E, Michoux L, Triballeau N, Lemoullec JM, Mollat P, Thauvin M, Prange T, Minet D, Clement-Lacroix P, Robin-Jagerschmidt C, Fleury D, Guedin D, Deprez P J Med Chem. 2012 Aug 16. PMID:22897611 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Androgen receptor 3D structures

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