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Yorodumi- PDB-5t8j: Synthesis and biological evaluation of novel selective androgen r... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5t8j | ||||||
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Title | Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives | ||||||
Components | Androgen receptor | ||||||
Keywords | HORMONE RECEPTOR / Androgen Receptor / selective androgen receptor modulators / SARMS | ||||||
Function / homology | Function and homology information male somatic sex determination / activation of prostate induction by androgen receptor signaling pathway / lateral sprouting involved in mammary gland duct morphogenesis / POU domain binding / negative regulation of integrin biosynthetic process / regulation of developmental growth / male genitalia morphogenesis / positive regulation of integrin biosynthetic process / tertiary branching involved in mammary gland duct morphogenesis / animal organ formation ...male somatic sex determination / activation of prostate induction by androgen receptor signaling pathway / lateral sprouting involved in mammary gland duct morphogenesis / POU domain binding / negative regulation of integrin biosynthetic process / regulation of developmental growth / male genitalia morphogenesis / positive regulation of integrin biosynthetic process / tertiary branching involved in mammary gland duct morphogenesis / animal organ formation / androgen binding / Leydig cell differentiation / regulation of systemic arterial blood pressure / epithelial cell morphogenesis / prostate gland growth / epithelial cell differentiation involved in prostate gland development / positive regulation of epithelial cell proliferation involved in prostate gland development / prostate gland epithelium morphogenesis / intracellular receptor signaling pathway / cellular response to testosterone stimulus / RNA polymerase II general transcription initiation factor binding / positive regulation of transcription by RNA polymerase III / positive regulation of insulin-like growth factor receptor signaling pathway / positive regulation of intracellular estrogen receptor signaling pathway / morphogenesis of an epithelial fold / cellular response to steroid hormone stimulus / seminiferous tubule development / androgen receptor signaling pathway / single fertilization / RUNX2 regulates osteoblast differentiation / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / regulation of protein localization to plasma membrane / intracellular steroid hormone receptor signaling pathway / positive regulation of phosphorylation / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / steroid binding / insulin-like growth factor receptor signaling pathway / epithelial cell proliferation / G protein-coupled receptor activity / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of cell differentiation / multicellular organism growth / SUMOylation of intracellular receptors / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / transcription coactivator binding / beta-catenin binding / positive regulation of miRNA transcription / Nuclear Receptor transcription pathway / male gonad development / nuclear receptor activity / negative regulation of epithelial cell proliferation / MAPK cascade / cell-cell signaling / positive regulation of NF-kappaB transcription factor activity / ATPase binding / spermatogenesis / DNA-binding transcription activator activity, RNA polymerase II-specific / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / positive regulation of MAPK cascade / molecular adaptor activity / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / Ub-specific processing proteases / nuclear speck / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of cell population proliferation / signaling receptor binding / chromatin binding / positive regulation of cell population proliferation / chromatin / positive regulation of gene expression / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Wilson, K.P. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2017 Title: Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives. Authors: Asano, M. / Hitaka, T. / Imada, T. / Yamada, M. / Morimoto, M. / Shinohara, H. / Hara, T. / Yamaoka, M. / Santou, T. / Nakayama, M. / Imai, Y. / Habuka, N. / Yano, J. / Wilson, K. / Fujita, H. / Hasuoka, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5t8j.cif.gz | 114.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5t8j.ent.gz | 92.7 KB | Display | PDB format |
PDBx/mmJSON format | 5t8j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t8/5t8j ftp://data.pdbj.org/pub/pdb/validation_reports/t8/5t8j | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 30150.270 Da / Num. of mol.: 1 / Fragment: UNP residues 132-388 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AR, DHTR, NR3C4 / Production host: Escherichia coli (E. coli) / References: UniProt: P10275 |
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#2: Chemical | ChemComp-GOL / |
#3: Chemical | ChemComp-77T / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.1 Å3/Da / Density % sol: 41.33 % / Mosaicity: 2.205 ° |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2 / Details: ~1M ammonium phosphate dibasic |
-Data collection
Diffraction | Mean temperature: 80 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.987 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 17, 2007 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.987 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.7→35.46 Å / Num. obs: 6138 / % possible obs: 87.2 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.092 / Χ2: 1.032 / Net I/av σ(I): 15.655 / Net I/σ(I): 15.2 / Num. measured all: 35922 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.7→35.46 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.883 / SU B: 43.871 / SU ML: 0.436 / SU R Cruickshank DPI: 0.3816 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.529 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 143.6 Å2 / Biso mean: 74.075 Å2 / Biso min: 41.72 Å2
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Refinement step | Cycle: final / Resolution: 2.7→35.46 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.701→2.771 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 19.8084 Å / Origin y: 5.2379 Å / Origin z: 11.1493 Å
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