[English] 日本語
Yorodumi
- PDB-5t8j: Synthesis and biological evaluation of novel selective androgen r... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5t8j
TitleSynthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives
ComponentsAndrogen receptor
KeywordsHORMONE RECEPTOR / Androgen Receptor / selective androgen receptor modulators / SARMS
Function / homology
Function and homology information


male somatic sex determination / prostate induction / lateral sprouting involved in mammary gland duct morphogenesis / male genitalia morphogenesis / POU domain binding / regulation of developmental growth / positive regulation of integrin biosynthetic process / tertiary branching involved in mammary gland duct morphogenesis / animal organ formation / androgen binding ...male somatic sex determination / prostate induction / lateral sprouting involved in mammary gland duct morphogenesis / male genitalia morphogenesis / POU domain binding / regulation of developmental growth / positive regulation of integrin biosynthetic process / tertiary branching involved in mammary gland duct morphogenesis / animal organ formation / androgen binding / cellular response to testosterone stimulus / regulation of systemic arterial blood pressure / Leydig cell differentiation / epithelial cell differentiation involved in prostate gland development / seminiferous tubule development / positive regulation of epithelial cell proliferation involved in prostate gland development / prostate gland epithelium morphogenesis / prostate gland growth / epithelial cell morphogenesis / membraneless organelle assembly / RNA polymerase II general transcription initiation factor binding / positive regulation of insulin-like growth factor receptor signaling pathway / positive regulation of transcription by RNA polymerase III / cellular response to steroid hormone stimulus / morphogenesis of an epithelial fold / positive regulation of intracellular estrogen receptor signaling pathway / androgen receptor signaling pathway / RUNX2 regulates osteoblast differentiation / nuclear steroid receptor activity / mammary gland alveolus development / cellular response to estrogen stimulus / estrogen response element binding / nuclear receptor-mediated steroid hormone signaling pathway / single fertilization / regulation of protein localization to plasma membrane / RNA polymerase II core promoter sequence-specific DNA binding / intracellular receptor signaling pathway / estrogen receptor signaling pathway / steroid binding / insulin-like growth factor receptor signaling pathway / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / epithelial cell proliferation / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of cell differentiation / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / molecular condensate scaffold activity / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / beta-catenin binding / Nuclear Receptor transcription pathway / positive regulation of miRNA transcription / transcription coactivator binding / multicellular organism growth / male gonad development / nuclear receptor activity / negative regulation of epithelial cell proliferation / cell-cell signaling / MAPK cascade / ATPase binding / DNA-binding transcription activator activity, RNA polymerase II-specific / spermatogenesis / molecular adaptor activity / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / DNA-binding transcription factor activity, RNA polymerase II-specific / Ub-specific processing proteases / transcription cis-regulatory region binding / positive regulation of MAPK cascade / nuclear speck / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / signaling receptor binding / negative regulation of cell population proliferation / positive regulation of cell population proliferation / chromatin binding / positive regulation of gene expression / chromatin / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / 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
Androgen receptor / Androgen receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors ...Androgen receptor / Androgen receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-77T / Androgen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsWilson, K.P.
CitationJournal: 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
DepositionSep 7, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 26, 2017Provider: repository / Type: Initial release
Revision 1.1Nov 6, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Androgen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,4913
Polymers30,1501
Non-polymers3402
Water91951
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)52.449, 65.675, 70.713
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Androgen receptor / Dihydrotestosterone receptor / Nuclear receptor subfamily 3 group C member 4


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
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-77T / 2-fluoro-4-[(2S,3S)-3-hydroxy-2,3-dimethylpyrrolidin-1-yl]-3-methylbenzonitrile


Mass: 248.296 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H17FN2O
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 51 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.1 Å3/Da / Density % sol: 41.33 % / Mosaicity: 2.205 °
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2 / Details: ~1M ammonium phosphate dibasic

-
Data collection

DiffractionMean temperature: 80 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.987 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 17, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.987 Å / Relative weight: 1
ReflectionResolution: 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
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.7-2.784.60.178158.5
2.78-2.874.80.148163.5
2.87-2.9750.144171
2.97-3.095.40.134175
3.09-3.235.20.129186.2
3.23-3.45.80.123191.5
3.4-3.616.10.117198.4
3.61-3.896.30.108199.7
3.89-4.296.60.091100
4.29-4.96.50.0751100
4.9-6.186.40.0691100
6.18-5060.088199.4

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
REFMAC5.8.0049refinement
PDB_EXTRACT3.2data extraction
MOLREPphasing
HKL-2000data reduction
RefinementMethod 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
RfactorNum. reflection% reflectionSelection details
Rfree0.3047 285 4.7 %RANDOM
Rwork0.1967 ---
obs0.2015 5820 86.06 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 143.6 Å2 / Biso mean: 74.075 Å2 / Biso min: 41.72 Å2
Baniso -1Baniso -2Baniso -3
1--0.38 Å20 Å20 Å2
2---1.01 Å20 Å2
3---1.38 Å2
Refinement stepCycle: final / Resolution: 2.7→35.46 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2033 0 24 51 2108
Biso mean--72.27 59.91 -
Num. residues----249
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0192109
X-RAY DIFFRACTIONr_bond_other_d0.0010.022033
X-RAY DIFFRACTIONr_angle_refined_deg1.1751.9622851
X-RAY DIFFRACTIONr_angle_other_deg0.69634663
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.3845248
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.923.46998
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.29215376
X-RAY DIFFRACTIONr_dihedral_angle_4_deg9.6581514
X-RAY DIFFRACTIONr_chiral_restr0.0550.2311
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0212333
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02512
X-RAY DIFFRACTIONr_mcbond_it1.8794.423995
X-RAY DIFFRACTIONr_mcbond_other1.8774.418994
X-RAY DIFFRACTIONr_mcangle_it3.1676.6241242
LS refinement shellResolution: 2.701→2.771 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.426 15 -
Rwork0.251 255 -
all-270 -
obs--52.33 %
Refinement TLS params.Method: refined / Origin x: 19.8084 Å / Origin y: 5.2379 Å / Origin z: 11.1493 Å
111213212223313233
T0.0492 Å2-0.0658 Å2-0.0642 Å2-0.1498 Å20.0267 Å2--0.2808 Å2
L2.1352 °2-0.4594 °2-0.5662 °2-3.426 °20.5738 °2--4.0651 °2
S0.0039 Å °0.0522 Å °0.0289 Å °-0.0085 Å °-0.0248 Å °-0.1042 Å °0.1587 Å °0.0383 Å °0.0209 Å °

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more