[English] 日本語
Yorodumi
- PDB-6nx1: STRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUN... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6nx1
TitleSTRUCTURE OF HUMAN PREGNANE X RECEPTOR LIGAND BINDING DOMAIN BOUND TETHERED WITH SRC CO-ACTIVATOR PEPTIDE AND COMPOUND-3 AKA 1,1,1,3,3,3-HEXAFLUORO-2-{4-[1-(4- LUOROBENZENESULFONYL)CYCLOPENTYL]PHENYL}PROPAN-2-OL
ComponentsNuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1 fusion
KeywordsTRANSFERASE / MULTIPLE BINDING MODES / XENOBIOTIC / PROMISCUOUS / NUCLEAR HORMONE RECEPTOR / PXR / RORgT
Function / homology
Function and homology information


xenobiotic transport / labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / intermediate filament cytoskeleton / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / steroid metabolic process ...xenobiotic transport / labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / intermediate filament cytoskeleton / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / steroid metabolic process / cellular response to Thyroglobulin triiodothyronine / estrous cycle / Synthesis of bile acids and bile salts / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / xenobiotic catabolic process / nuclear retinoid X receptor binding / response to retinoic acid / histone acetyltransferase activity / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / histone acetyltransferase / cellular response to hormone stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / lactation / positive regulation of neuron differentiation / Regulation of lipid metabolism by PPARalpha / xenobiotic metabolic process / cerebellum development / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / response to progesterone / nuclear estrogen receptor binding / hippocampus development / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / male gonad development / sequence-specific double-stranded DNA binding / Circadian Clock / response to estradiol / HATs acetylate histones / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / transcription coactivator activity / cell differentiation / nuclear body / protein dimerization activity / DNA-binding transcription factor activity, RNA polymerase II-specific / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / chromatin binding / chromatin / regulation of DNA-templated transcription / positive regulation of gene expression / positive regulation of DNA-templated transcription / 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
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 / Steroid 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 / PAS domain / Nuclear receptor coactivator, interlocking / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone 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-L7D / Nuclear receptor subfamily 1 group I member 2 / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.27 Å
AuthorsKhan, J.A.
CitationJournal: Acs Med.Chem.Lett. / Year: 2019
Title: Structure-based Discovery of Phenyl (3-Phenylpyrrolidin-3-yl)sulfones as Selective, Orally Active ROR gamma t Inverse Agonists.
Authors: Duan, J.J. / Lu, Z. / Jiang, B. / Stachura, S. / Weigelt, C.A. / Sack, J.S. / Khan, J. / Ruzanov, M. / Galella, M.A. / Wu, D.R. / Yarde, M. / Shen, D.R. / Shuster, D.J. / Borowski, V. / Xie, ...Authors: Duan, J.J. / Lu, Z. / Jiang, B. / Stachura, S. / Weigelt, C.A. / Sack, J.S. / Khan, J. / Ruzanov, M. / Galella, M.A. / Wu, D.R. / Yarde, M. / Shen, D.R. / Shuster, D.J. / Borowski, V. / Xie, J.H. / Zhang, L. / Vanteru, S. / Gupta, A.K. / Mathur, A. / Zhao, Q. / Foster, W. / Salter-Cid, L.M. / Carter, P.H. / Dhar, T.G.M.
History
DepositionFeb 7, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 12, 2020Provider: repository / Type: Initial release
Revision 1.1Apr 22, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name
Revision 1.2Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)80,7324
Polymers79,7912
Non-polymers9412
Water1,09961
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area860 Å2
ΔGint-4 kcal/mol
Surface area27530 Å2
2
A: Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1 fusion
hetero molecules

B: Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1 fusion
hetero molecules


Theoretical massNumber of molelcules
Total (without water)80,7324
Polymers79,7912
Non-polymers9412
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_544-x,y-1/2,-z-1/21
Buried area1820 Å2
ΔGint-15 kcal/mol
Surface area26580 Å2
MethodPISA
Unit cell
Length a, b, c (Å)84.195, 89.612, 106.158
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1 fusion / 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 / 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: 39895.633 Da / Num. of mol.: 2 / Fragment: LIGAND BINDING DOMAIN
Source method: isolated from a genetically manipulated source
Details: PXR-LBD(130-434)WITH TETHERED SRC DOMAIN(678-710) / Source: (gene. exp.) Homo sapiens (human) / Gene: NR1I2, PXR, NCOA1, BHLHE74, SRC1 / Plasmid: pET28 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: O75469, UniProt: Q15788, histone acetyltransferase
#2: Chemical ChemComp-L7D / 1,1,1,3,3,3-hexafluoro-2-(4-{1-[(4-fluorophenyl)sulfonyl]cyclopentyl}phenyl)propan-2-ol


Mass: 470.401 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H17F7O3S
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 61 / 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: 2.51 Å3/Da / Density % sol: 50.99 %
Crystal growTemperature: 296 K / Method: vapor diffusion, hanging drop
Details: 0.1M Hepes pH 7.5, 150mM NaCl, 10-15%(V/V)PEG10K, Crystals were cryoprotected by supplementing the mother liquor with 15% (v/v) ethylene glycol and harvested by flash-cooling in liquid nitrogen
PH range: 7.5- 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 1 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Sep 15, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.27→50 Å / Num. obs: 37903 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 6.1 % / Biso Wilson estimate: 58.38 Å2 / Rmerge(I) obs: 0.054 / Rsym value: 0.02 / Net I/σ(I): 28.9
Reflection shellResolution: 2.27→2.35 Å / Redundancy: 5.8 % / Rmerge(I) obs: 0.437 / Mean I/σ(I) obs: 3.8 / % possible all: 99.8

-
Processing

Software
NameVersionClassification
BUSTER2.11.2refinement
PDB_EXTRACT3.24data extraction
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementResolution: 2.27→42.1 Å / Cor.coef. Fo:Fc: 0.9442 / Cor.coef. Fo:Fc free: 0.924 / SU R Cruickshank DPI: 0.236 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.232 / SU Rfree Blow DPI: 0.188 / SU Rfree Cruickshank DPI: 0.191
RfactorNum. reflection% reflectionSelection details
Rfree0.2397 1881 4.99 %RANDOM
Rwork0.2107 ---
obs0.2122 37732 99.85 %-
Displacement parametersBiso max: 166.73 Å2 / Biso mean: 62.86 Å2 / Biso min: 20 Å2
Baniso -1Baniso -2Baniso -3
1--6.6612 Å20 Å20 Å2
2--0.2395 Å20 Å2
3---6.4217 Å2
Refine analyzeLuzzati coordinate error obs: 0.321 Å
Refinement stepCycle: final / Resolution: 2.27→42.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4526 0 87 61 4674
Biso mean--75.51 55.83 -
Num. residues----582
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1617SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes95HARMONIC2
X-RAY DIFFRACTIONt_gen_planes722HARMONIC5
X-RAY DIFFRACTIONt_it4734HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion620SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact5489SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4734HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg6438HARMONIC21.02
X-RAY DIFFRACTIONt_omega_torsion2.58
X-RAY DIFFRACTIONt_other_torsion18.64
LS refinement shellResolution: 2.27→2.33 Å / Rfactor Rfree error: 0 / Total num. of bins used: 19
RfactorNum. reflection% reflection
Rfree0.2437 143 5 %
Rwork0.2384 2718 -
all0.2386 2861 -
obs--99.85 %

+
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