[English] 日本語
Yorodumi
- PDB-6k5o: Development of Novel Lithocholic Acid Derivatives as Vitamin D Re... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6k5o
TitleDevelopment of Novel Lithocholic Acid Derivatives as Vitamin D Receptor Agonists
Components
  • Mediator of RNA polymerase II transcription subunit 1
  • Vitamin D3 receptor
KeywordsTRANSCRIPTION / VITAMIN D RECEPTOR
Function / homology
Function and homology information


negative regulation of bone trabecula formation / positive regulation of parathyroid hormone secretion / mammary gland branching involved in pregnancy / Vitamin D (calciferol) metabolism / retinal pigment epithelium development / positive regulation of apoptotic process involved in mammary gland involution / androgen biosynthetic process / regulation of RNA biosynthetic process / SUMOylation of intracellular receptors / Nuclear Receptor transcription pathway ...negative regulation of bone trabecula formation / positive regulation of parathyroid hormone secretion / mammary gland branching involved in pregnancy / Vitamin D (calciferol) metabolism / retinal pigment epithelium development / positive regulation of apoptotic process involved in mammary gland involution / androgen biosynthetic process / regulation of RNA biosynthetic process / SUMOylation of intracellular receptors / Nuclear Receptor transcription pathway / thyroid hormone receptor signaling pathway / response to bile acid / dense fibrillar component / cellular response to vitamin D / lens development in camera-type eye / calcitriol binding / lithocholic acid binding / nuclear receptor-mediated bile acid signaling pathway / bile acid nuclear receptor activity / ventricular trabecula myocardium morphogenesis / intestinal absorption / negative regulation of ossification / megakaryocyte development / negative regulation of keratinocyte proliferation / vitamin D binding / Generic Transcription Pathway / mediator complex / nuclear retinoic acid receptor binding / positive regulation of keratinocyte differentiation / response to aldosterone / cellular response to thyroid hormone stimulus / vitamin D receptor signaling pathway / positive regulation of vitamin D receptor signaling pathway / phosphate ion transmembrane transport / peroxisome proliferator activated receptor binding / nuclear vitamin D receptor binding / negative regulation of neuron differentiation / nuclear thyroid hormone receptor binding / cellular response to steroid hormone stimulus / histone acetyltransferase binding / LBD domain binding / decidualization / RSV-host interactions / erythrocyte development / regulation of calcium ion transport / keratinocyte differentiation / nuclear receptor-mediated steroid hormone signaling pathway / skeletal system development / positive regulation of transcription initiation by RNA polymerase II / general transcription initiation factor binding / fat cell differentiation / nuclear retinoid X receptor binding / lactation / ubiquitin ligase complex / retinoic acid receptor signaling pathway / cell morphogenesis / RNA polymerase II preinitiation complex assembly / intracellular receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / animal organ morphogenesis / heterochromatin / positive regulation of erythrocyte differentiation / BMAL1:CLOCK,NPAS2 activates circadian expression / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / Activation of gene expression by SREBF (SREBP) / T-tubule / apoptotic signaling pathway / cellular response to epidermal growth factor stimulus / nuclear estrogen receptor binding / nuclear receptor binding / RNA polymerase II transcription regulator complex / Heme signaling / positive regulation of transcription elongation by RNA polymerase II / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / promoter-specific chromatin binding / response to calcium ion / euchromatin / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / protein-DNA complex / chromatin DNA binding / caveola / mRNA transcription by RNA polymerase II / intracellular calcium ion homeostasis / nuclear receptor activity / cellular response to amyloid-beta / transcription coregulator activity / heart development / calcium ion transport / nuclear matrix / transcription coactivator binding / transcription corepressor activity / response to estradiol / ubiquitin protein ligase activity / angiogenesis / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / DNA-binding transcription factor binding
Similarity search - Function
: / Mediator complex, subunit Med1 / Mediator of RNA polymerase II transcription subunit 1 / Vitamin D receptor / VDR, DNA-binding domain / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. ...: / Mediator complex, subunit Med1 / Mediator of RNA polymerase II transcription subunit 1 / Vitamin D receptor / VDR, DNA-binding domain / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone 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-D0O / Vitamin D3 receptor / Mediator of RNA polymerase II transcription subunit 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsMasuno, H. / Kagechika, H. / Ito, N.
Funding support Japan, 3items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science15K08018 Japan
Japan Society for the Promotion of Science16K08318 Japan
Japan Society for the Promotion of Science17H03997 Japan
CitationJournal: Bioorg.Med.Chem. / Year: 2019
Title: Development of novel lithocholic acid derivatives as vitamin D receptor agonists.
Authors: Masuno, H. / Kazui, Y. / Tanatani, A. / Fujii, S. / Kawachi, E. / Ikura, T. / Ito, N. / Yamamoto, K. / Kagechika, H.
History
DepositionMay 29, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 24, 2019Provider: repository / Type: Initial release
Revision 1.1Aug 14, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Nov 22, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Vitamin D3 receptor
C: Mediator of RNA polymerase II transcription subunit 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,6213
Polymers32,1662
Non-polymers4551
Water46826
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: native gel electrophoresis
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1020 Å2
ΔGint-9 kcal/mol
Surface area11590 Å2
MethodPISA
Unit cell
Length a, b, c (Å)153.884, 43.690, 41.792
Angle α, β, γ (deg.)90.00, 96.05, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Vitamin D3 receptor / VDR / 1 / 25-dihydroxyvitamin D3 receptor / Nuclear receptor subfamily 1 group I member 1


Mass: 30595.037 Da / Num. of mol.: 1 / Mutation: 165-211 deletion
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Vdr, Nr1i1 / Production host: Escherichia coli (E. coli) / References: UniProt: P13053
#2: Protein/peptide Mediator of RNA polymerase II transcription subunit 1 / Activator-recruited cofactor 205 kDa component / ARC205 / Mediator complex subunit 1 / Peroxisome ...Activator-recruited cofactor 205 kDa component / ARC205 / Mediator complex subunit 1 / Peroxisome proliferator-activated receptor-binding protein / PPAR-binding protein / Thyroid hormone receptor-associated protein complex 220 kDa component / Trap220 / Thyroid receptor-interacting protein 2 / TRIP-2 / Vitamin D receptor-interacting protein complex component DRIP205 / p53 regulatory protein RB18A


Mass: 1570.898 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15648
#3: Chemical ChemComp-D0O / (4~{R})-4-[(3~{R},5~{R},8~{R},9~{S},10~{S},13~{R},14~{S},17~{R})-10,13-dimethyl-3-methylsulfonyloxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]pentanoic acid


Mass: 454.663 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H42O5S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 26 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.17 Å3/Da / Density % sol: 43.36 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 0.1M MOPS/NaOH (pH 7.0), 0.1-0.4 M sodium formate, 12-22% (w/v) PEG4000, and 5% (v/v) ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Photon Factory / Beamline: BL-6A / Wavelength: 0.978 Å
DetectorType: ADSC QUANTUM 4r / Detector: CCD / Date: Jun 12, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. obs: 25497 / % possible obs: 98.6 % / Redundancy: 3.5 % / Rmerge(I) obs: 0.043 / Net I/σ(I): 16.3
Reflection shellResolution: 1.8→1.83 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.76 / Mean I/σ(I) obs: 1.28 / Num. unique obs: 1198 / CC1/2: 0.796 / % possible all: 91.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0222refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2ZLC

2zlc


Resolution: 1.8→35.01 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.949 / SU B: 6.727 / SU ML: 0.172 / Cross valid method: THROUGHOUT / ESU R: 0.138 / ESU R Free: 0.137 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25672 1214 4.8 %RANDOM
Rwork0.21116 ---
obs0.21324 24273 98.37 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 41.527 Å2
Baniso -1Baniso -2Baniso -3
1--4.19 Å20 Å2-0.97 Å2
2--6.32 Å20 Å2
3----1.88 Å2
Refinement stepCycle: 1 / Resolution: 1.8→35.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1984 0 31 26 2041
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0142059
X-RAY DIFFRACTIONr_bond_other_d0.0010.0171916
X-RAY DIFFRACTIONr_angle_refined_deg1.4061.6762789
X-RAY DIFFRACTIONr_angle_other_deg0.9281.6624510
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.685244
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.56422.941102
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.9115378
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.0331511
X-RAY DIFFRACTIONr_chiral_restr0.070.2274
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.022203
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02341
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.9574.071985
X-RAY DIFFRACTIONr_mcbond_other2.944.07984
X-RAY DIFFRACTIONr_mcangle_it4.1736.0851226
X-RAY DIFFRACTIONr_mcangle_other4.1756.0871227
X-RAY DIFFRACTIONr_scbond_it3.5964.4471074
X-RAY DIFFRACTIONr_scbond_other3.5954.4481075
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.4736.5051564
X-RAY DIFFRACTIONr_long_range_B_refined6.39147.9832299
X-RAY DIFFRACTIONr_long_range_B_other6.39647.9852300
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.799→1.845 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.423 88 -
Rwork0.384 1593 -
obs--89.89 %

+
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