[English] 日本語
Yorodumi
- PDB-8f5y: Crystal structure of pregnane X receptor ligand binding domain co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8f5y
TitleCrystal structure of pregnane X receptor ligand binding domain complexed with JQ1
Components
  • Nuclear receptor coactivator 1
  • Nuclear receptor subfamily 1 group I member 2
KeywordsTRANSCRIPTION / nuclear receptor / transcription factor / metabolism / antibiotic
Function / homology
Function and homology information


cellular response to molecule of bacterial origin / intestinal epithelial structure maintenance / intermediate filament cytoskeleton / labyrinthine layer morphogenesis / positive regulation of transcription from RNA polymerase II promoter by galactose / regulation of thyroid hormone receptor signaling pathway / positive regulation of female receptivity / xenobiotic transport / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / hypothalamus development ...cellular response to molecule of bacterial origin / intestinal epithelial structure maintenance / intermediate filament cytoskeleton / labyrinthine layer morphogenesis / positive regulation of transcription from RNA polymerase II promoter by galactose / regulation of thyroid hormone receptor signaling pathway / positive regulation of female receptivity / xenobiotic transport / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / hypothalamus development / male mating behavior / steroid metabolic process / cellular response to Thyroglobulin triiodothyronine / Synthesis of bile acids and bile salts / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / xenobiotic catabolic process / response to retinoic acid / progesterone receptor signaling pathway / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / cellular response to hormone stimulus / histone H4K16 acetyltransferase activity / histone H3K56 acetyltransferase activity / histone H3K23 acetyltransferase activity / histone H2AK5 acetyltransferase activity / histone H2AK9 acetyltransferase activity / histone H2BK5 acetyltransferase activity / histone H2BK12 acetyltransferase activity / histone H3K4 acetyltransferase activity / histone H3K27 acetyltransferase activity / histone H3K36 acetyltransferase activity / histone H3K122 acetyltransferase activity / histone H3K18 acetyltransferase activity / histone H3K9 acetyltransferase activity / histone H3K14 acetyltransferase activity / histone H4K5 acetyltransferase activity / histone H4K8 acetyltransferase activity / histone H4K12 acetyltransferase activity / Recycling of bile acids and salts / histone acetyltransferase / estrous cycle / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / intracellular receptor signaling pathway / estrogen receptor signaling pathway / positive regulation of adipose tissue development / : / lactation / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / regulation of cellular response to insulin stimulus / xenobiotic metabolic process / positive regulation of neuron differentiation / cerebellum development / BMAL1:CLOCK,NPAS2 activates circadian expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / hippocampus development / response to progesterone / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / nuclear estrogen receptor binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Heme signaling / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / RNA polymerase II transcription regulator complex / nuclear receptor activity / male gonad development / sequence-specific double-stranded DNA binding / : / response to estradiol / HATs acetylate histones / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / DNA-binding transcription activator activity, RNA polymerase II-specific / transcription regulator complex / Estrogen-dependent gene expression / cell differentiation / transcription coactivator activity / DNA-binding transcription factor activity, RNA polymerase II-specific / protein dimerization activity / nuclear body / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of gene expression / regulation of DNA-templated transcription / protein-containing complex binding / chromatin / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II
Similarity search - Function
Nuclear receptor coactivator 1 / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain / Nuclear receptor coactivator / : ...Nuclear receptor coactivator 1 / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain / Nuclear receptor coactivator / : / Steroid receptor coactivator / Unstructured region on nuclear receptor coactivator protein / Nuclear receptor coactivators bHLH domain / PAS domain / Nuclear receptor coactivator, interlocking / : / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / Helix-loop-helix DNA-binding domain superfamily / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / 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
Similarity search - Domain/homology
Chem-JQ1 / Nuclear receptor subfamily 1 group I member 2 / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsHuber, A.D. / Poudel, S. / Seetharaman, J. / Miller, D.J. / Chen, T.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM118041 United States
CitationJournal: Nucleic Acids Res. / Year: 2024
Title: A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR.
Authors: Huber, A.D. / Poudel, S. / Wu, J. / Miller, D.J. / Lin, W. / Yang, L. / Bwayi, M.N. / Rimmer, M.A. / Gee, R.R.F. / Seetharaman, J. / Chai, S.C. / Chen, T.
History
DepositionNov 15, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 21, 2024Provider: repository / Type: Initial release
Revision 1.1Mar 6, 2024Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Nuclear receptor subfamily 1 group I member 2
B: Nuclear receptor subfamily 1 group I member 2
C: Nuclear receptor coactivator 1
D: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)78,9466
Polymers78,0304
Non-polymers9162
Water1,72996
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3970 Å2
ΔGint-31 kcal/mol
Surface area25180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)75.547, 82.562, 103.669
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and (resid 142 through 144 or (resid 145...
d_2ens_1(chain "B" and (resid 142 through 169 or resid 171...
d_1ens_2(chain "C" and resid 685 through 695)
d_2ens_2(chain "D" and (resid 685 through 687 or (resid 688...

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ens_1GLYGLYPHEPHEAA142 - 16924 - 51
d_12ens_1ASNASNGLYGLYAA171 - 17653 - 58
d_13ens_1LYSLYSVALVALAA210 - 21192 - 93
d_14ens_1LEULEUGLUGLUAA213 - 21895 - 100
d_15ens_1GLYGLYTYRTYRAA220 - 225102 - 107
d_16ens_1PROPROPROPROAA227 - 228109 - 110
d_17ens_1SERSERILEILEAA238 - 269120 - 151
d_18ens_1ASPASPLEULEUAA271 - 283153 - 165
d_19ens_1GLNGLNTYRTYRAA285 - 306167 - 188
d_110ens_1LEULEULEULEUAA308190
d_111ens_1GLUGLUTYRTYRAA321 - 328203 - 210
d_112ens_1LEULEUGLNGLNAA330 - 358212 - 240
d_113ens_1ARGARGGLNGLNAA360 - 366242 - 248
d_114ens_1GLNGLNHISHISAA368 - 386250 - 268
d_115ens_1PHEPHEALAALAAA388 - 405270 - 287
d_116ens_1THRTHRTHRTHRAA408290
d_117ens_1LEULEULEULEUAA411 - 412293 - 294
d_118ens_1ILEILEILEILEAA414 - 431296 - 313
d_119ens_1JQ1JQ1JQ1JQ1AE501
d_21ens_1GLYGLYPHEPHEBB142 - 16924 - 51
d_22ens_1ASNASNGLYGLYBB171 - 17653 - 58
d_23ens_1LYSLYSVALVALBB210 - 21192 - 93
d_24ens_1LEULEUGLUGLUBB213 - 21895 - 100
d_25ens_1GLYGLYTYRTYRBB220 - 225102 - 107
d_26ens_1PROPROILEILEBB227 - 269109 - 151
d_27ens_1ASPASPLEULEUBB271 - 283153 - 165
d_28ens_1GLNGLNTYRTYRBB285 - 306167 - 188
d_29ens_1LEULEUTYRTYRBB308 - 328190 - 210
d_210ens_1LEULEUGLNGLNBB330 - 358212 - 240
d_211ens_1ARGARGGLNGLNBB360 - 366242 - 248
d_212ens_1GLNGLNHISHISBB368 - 386250 - 268
d_213ens_1PHEPHEALAALABB388 - 405270 - 287
d_214ens_1THRTHRTHRTHRBB408290
d_215ens_1LEULEULEULEUBB411 - 412293 - 294
d_216ens_1ILEILEILEILEBB414 - 431296 - 313
d_217ens_1JQ1JQ1JQ1JQ1BF501
d_11ens_2GLUGLUGLNGLNCC685 - 69510 - 20
d_21ens_2GLUGLUGLNGLNDD685 - 69510 - 20

NCS ensembles :
ID
ens_1
ens_2

NCS oper: (Code: givenMatrix: (-0.976090086405, 0.128059925713, 0.175638260775), (0.190698317067, 0.116716515788, 0.974685286033), (0.104318239486, 0.984874565805, -0.138346646297)Vector: 54. ...NCS oper: (Code: given
Matrix: (-0.976090086405, 0.128059925713, 0.175638260775), (0.190698317067, 0.116716515788, 0.974685286033), (0.104318239486, 0.984874565805, -0.138346646297)
Vector: 54.3294286431, 5.71443112547, -15.769759111)

-
Components

#1: Protein Nuclear receptor subfamily 1 group I member 2 / Orphan nuclear receptor PAR1 / Orphan nuclear receptor PXR / Pregnane X receptor / Steroid and ...Orphan nuclear receptor PAR1 / Orphan nuclear receptor PXR / Pregnane X receptor / Steroid and xenobiotic receptor / SXR


Mass: 36208.742 Da / Num. of mol.: 2 / Fragment: UNP residues 153-457
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1I2, PXR / Production host: Escherichia coli (E. coli) / References: UniProt: O75469
#2: Protein/peptide Nuclear receptor coactivator 1 / NCoA-1 / Class E basic helix-loop-helix protein 74 / bHLHe74 / Protein Hin-2 / RIP160 / Renal ...NCoA-1 / Class E basic helix-loop-helix protein 74 / bHLHe74 / Protein Hin-2 / RIP160 / Renal carcinoma antigen NY-REN-52 / Steroid receptor coactivator 1 / SRC-1


Mass: 2806.163 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15788, histone acetyltransferase
#3: Chemical ChemComp-JQ1 / (6S)-6-(2-tert-butoxy-2-oxoethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6,7-dihydrothieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-10-ium


Mass: 457.996 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H26ClN4O2S / Feature type: SUBJECT OF INVESTIGATION / Comment: inhibitor*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 96 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.11 Å3/Da / Density % sol: 41.7 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 50 mM imidazole pH 7.0, 8% isopropanol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.9201 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: May 27, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9201 Å / Relative weight: 1
ReflectionResolution: 2.15→43.9 Å / Num. obs: 36061 / % possible obs: 99.8 % / Redundancy: 6.7 % / Biso Wilson estimate: 40.34 Å2 / CC1/2: 0.999 / Rsym value: 0.084 / Net I/σ(I): 12.9
Reflection shellResolution: 2.15→2.21 Å / Redundancy: 6.3 % / Mean I/σ(I) obs: 2.3 / Num. unique obs: 2900 / CC1/2: 0.829 / Rsym value: 0.797 / % possible all: 98.7

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
PDB_EXTRACTdata extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1NRL

1nrl


Resolution: 2.15→32.61 Å / SU ML: 0.2655 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 23.3715
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2155 1726 4.8 %
Rwork0.2067 34259 -
obs0.2071 35985 99.8 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 49.28 Å2
Refinement stepCycle: LAST / Resolution: 2.15→32.61 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4318 0 62 96 4476
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00714524
X-RAY DIFFRACTIONf_angle_d0.93346124
X-RAY DIFFRACTIONf_chiral_restr0.0587672
X-RAY DIFFRACTIONf_plane_restr0.0077776
X-RAY DIFFRACTIONf_dihedral_angle_d15.57641644
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAX-RAY DIFFRACTIONTorsion NCS1.06864664366
ens_2d_2CCX-RAY DIFFRACTIONTorsion NCS1.18922093853
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.15-2.210.32961410.27922799X-RAY DIFFRACTION98.76
2.21-2.280.29191400.25792798X-RAY DIFFRACTION99.9
2.28-2.360.25961400.23552817X-RAY DIFFRACTION99.93
2.36-2.460.24771480.23412814X-RAY DIFFRACTION99.9
2.46-2.570.27981440.23492821X-RAY DIFFRACTION100
2.57-2.710.28291510.24322831X-RAY DIFFRACTION100
2.71-2.880.25071700.22512826X-RAY DIFFRACTION99.93
2.88-3.10.22951300.22852852X-RAY DIFFRACTION100
3.1-3.410.23121220.22592877X-RAY DIFFRACTION99.87
3.41-3.90.19161260.19382900X-RAY DIFFRACTION99.8
3.9-4.910.16771580.16712906X-RAY DIFFRACTION99.84
4.91-32.610.19161560.19213018X-RAY DIFFRACTION99.69

+
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