[English] 日本語
Yorodumi
- PDB-5v8q: Synthesis and biological evaluation of novel selective androgen r... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5v8q
TitleSynthesis and biological evaluation of novel selective androgen receptor modulators (SARMs): Part III
ComponentsAndrogen receptor
KeywordsSIGNALING PROTEIN / Androgen Receptor / selective androgen receptor modulators / SARMS
Function / homology
Function and homology information


male somatic sex determination / : / 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 / intracellular receptor signaling pathway / tertiary branching involved in mammary gland duct morphogenesis ...male somatic sex determination / : / 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 / intracellular receptor signaling pathway / 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 / membraneless organelle assembly / prostate gland epithelium morphogenesis / cellular response to testosterone stimulus / RNA polymerase II general transcription initiation factor binding / positive regulation of insulin-like growth factor receptor signaling pathway / positive regulation of intracellular estrogen receptor signaling pathway / positive regulation of transcription by RNA polymerase III / cellular response to steroid hormone stimulus / morphogenesis of an epithelial fold / seminiferous tubule development / androgen receptor signaling pathway / RUNX2 regulates osteoblast differentiation / single fertilization / mammary gland alveolus development / regulation of protein localization to plasma membrane / cellular response to estrogen stimulus / estrogen response element binding / nuclear receptor-mediated steroid hormone signaling pathway / positive regulation of phosphorylation / estrogen receptor signaling pathway / 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 / negative regulation of extrinsic apoptotic signaling pathway / G protein-coupled receptor activity / positive regulation of cell differentiation / molecular condensate scaffold activity / SUMOylation of intracellular receptors / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / multicellular organism growth / beta-catenin binding / transcription coactivator 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 / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / signaling receptor binding / chromatin binding / positive regulation of cell population proliferation / positive regulation of gene expression / chromatin / 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
Androgen receptor / Androgen receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Zinc finger, C4 type (two domains) / 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 / Zinc finger, C4 type (two domains) / 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-97A / Androgen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.44 Å
AuthorsWilson, K.P.
CitationJournal: Bioorg. Med. Chem. / Year: 2017
Title: Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2f as a clinical candidate.
Authors: Aikawa, K. / Asano, M. / Ono, K. / Habuka, N. / Yano, J. / Wilson, K. / Fujita, H. / Kandori, H. / Hara, T. / Morimoto, M. / Santou, T. / Yamaoka, M. / Nakayama, M. / Hasuoka, A.
History
DepositionMar 22, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 24, 2017Provider: repository / Type: Initial release
Revision 1.1Jun 7, 2017Group: Data collection / Database references
Revision 1.2Nov 22, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Oct 30, 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)29,5635
Polymers28,9881
Non-polymers5754
Water2,864159
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)54.747, 65.557, 70.941
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: 28987.973 Da / Num. of mol.: 1 / Fragment: UNP residues 140-388
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.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-97A / 4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile


Mass: 298.260 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H13F3N2O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 159 / 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: 2.2 Å3/Da / Density % sol: 43.98 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.1
Details: 1.08M Phosphate NH4 Dibasic 0.07M Phosphate K Dibasic 0.03M Phosphate Na Monobasic pH 7.1

-
Data collection

DiffractionMean temperature: 80 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 23, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 1.44→36.15 Å / Num. obs: 46924 / % possible obs: 99.6 % / Redundancy: 4.6 % / Rmerge(I) obs: 0.04 / Χ2: 1.306 / Net I/σ(I): 16.1 / Num. measured all: 214273
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsΧ2Diffraction-ID% possible all
1.44-1.4640.6590.774197
1.46-1.494.30.5620.797199.3
1.49-1.524.50.4580.804199.9
1.52-1.554.70.3830.826199.9
1.55-1.584.60.3260.873199.9
1.58-1.624.70.2710.8631100
1.62-1.664.70.2140.9051100
1.66-1.714.70.1840.9581100
1.71-1.764.70.1511.0121100
1.76-1.814.70.121.0651100
1.81-1.884.70.0961.084199.9
1.88-1.954.70.0791.2371100
1.95-2.044.70.0581.2431100
2.04-2.154.70.0471.3591100
2.15-2.294.70.0441.593199.8
2.29-2.464.60.0462.1841100
2.46-2.714.50.0462.674199.4
2.71-3.14.50.0412.604199.6
3.1-3.914.40.0261.643199.8
3.91-504.40.0241.529196.9

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
HKL-2000data scaling
REFMAC5.8.0049refinement
PDB_EXTRACT3.22data extraction
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.44→36.15 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.957 / SU B: 2.565 / SU ML: 0.044 / SU R Cruickshank DPI: 0.0763 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.076 / ESU R Free: 0.068
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2047 2368 5.1 %RANDOM
Rwork0.1673 ---
obs0.1691 44484 99.44 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 51.85 Å2 / Biso mean: 22.497 Å2 / Biso min: 12.86 Å2
Baniso -1Baniso -2Baniso -3
1--0.01 Å20 Å20 Å2
2---0.21 Å20 Å2
3---0.22 Å2
Refinement stepCycle: final / Resolution: 1.44→36.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2033 0 60 159 2252
Biso mean--24.55 31.91 -
Num. residues----249
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.0192204
X-RAY DIFFRACTIONr_bond_other_d0.0010.022127
X-RAY DIFFRACTIONr_angle_refined_deg1.0811.9812996
X-RAY DIFFRACTIONr_angle_other_deg0.75134896
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.5055268
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.08823.6100
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.46415396
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.7831514
X-RAY DIFFRACTIONr_chiral_restr0.0620.2331
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212434
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02524
X-RAY DIFFRACTIONr_rigid_bond_restr1.65734331
X-RAY DIFFRACTIONr_sphericity_free18.289545
X-RAY DIFFRACTIONr_sphericity_bonded4.52354384
LS refinement shellResolution: 1.438→1.475 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.26 191 -
Rwork0.24 3129 -
all-3320 -
obs--96.29 %
Refinement TLS params.Method: refined / Origin x: 20.625 Å / Origin y: 5.4038 Å / Origin z: 11.0754 Å
111213212223313233
T0.0081 Å2-0.0074 Å2-0.0106 Å2-0.0076 Å20.0111 Å2--0.017 Å2
L0.8677 °2-0.2226 °2-0.4668 °2-1.0871 °20.3253 °2--1.6708 °2
S0.001 Å °-0.0027 Å °-0.0248 Å °0.0382 Å °-0.0161 Å °-0.0108 Å °0.032 Å °-0.0065 Å °0.0151 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