[English] 日本語
Yorodumi
- PDB-6hty: PXR in complex with P2X4 inhibitor compound 25 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6hty
TitlePXR in complex with P2X4 inhibitor compound 25
ComponentsNuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1
KeywordsTRANSCRIPTION / PXR / SRC-1 / CYP3A4 Induction
Function / homology
Function and homology information


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 / intermediate filament cytoskeleton / xenobiotic transport / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / hypothalamus development / steroid metabolic process ...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 / intermediate filament cytoskeleton / xenobiotic transport / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / hypothalamus development / 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 / xenobiotic catabolic process / nuclear retinoid X receptor binding / progesterone receptor signaling pathway / response to retinoic acid / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / 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 / cellular response to hormone stimulus / estrous cycle / Recycling of bile acids and salts / histone acetyltransferase / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / 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 / cerebellum development / positive regulation of neuron differentiation / 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 / nuclear estrogen receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA 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 / 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 / : / 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 / transcription coactivator activity / cell differentiation / DNA-binding transcription factor activity, RNA polymerase II-specific / nuclear body / protein dimerization activity / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / positive regulation of gene expression / chromatin binding / 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 / protein-containing complex / zinc ion binding
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 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 / Retinoid X Receptor / Retinoid X Receptor / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-GRH / Nuclear receptor subfamily 1 group I member 2 / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.22 Å
AuthorsHillig, R.C. / Puetter, V. / Werner, S. / Mesch, S. / Laux-Biehlmann, A. / Braeuer, N. / Dahloef, H. / Klint, J. / ter Laak, A. / Pook, E. ...Hillig, R.C. / Puetter, V. / Werner, S. / Mesch, S. / Laux-Biehlmann, A. / Braeuer, N. / Dahloef, H. / Klint, J. / ter Laak, A. / Pook, E. / Neagoe, I. / Nubbemeyer, R. / Schulz, S.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Discovery and Characterization of the Potent and Selective P2X4 InhibitorN-[4-(3-Chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and Structure-Guided Amelioration of Its CYP3A4 Induction Profile.
Authors: Werner, S. / Mesch, S. / Hillig, R.C. / Ter Laak, A. / Klint, J. / Neagoe, I. / Laux-Biehlmann, A. / Dahllof, H. / Brauer, N. / Puetter, V. / Nubbemeyer, R. / Schulz, S. / Bairlein, M. / ...Authors: Werner, S. / Mesch, S. / Hillig, R.C. / Ter Laak, A. / Klint, J. / Neagoe, I. / Laux-Biehlmann, A. / Dahllof, H. / Brauer, N. / Puetter, V. / Nubbemeyer, R. / Schulz, S. / Bairlein, M. / Zollner, T.M. / Steinmeyer, A.
History
DepositionOct 5, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 8, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Jan 24, 2024Group: 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 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)79,2829
Polymers78,3682
Non-polymers9147
Water2,666148
1
A: Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,5115
Polymers39,1841
Non-polymers3264
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,7714
Polymers39,1841
Non-polymers5873
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)85.417, 88.616, 104.929
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: GLY / Beg label comp-ID: GLY / End auth comp-ID: SER / End label comp-ID: SER / Refine code: _ / Auth seq-ID: 142 - 460 / Label seq-ID: 24 - 342

Dom-IDAuth asym-IDLabel asym-ID
1AA
2BB

-
Components

#1: Protein Nuclear receptor subfamily 1 group I member 2,Nuclear receptor coactivator 1 / 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: 39184.035 Da / Num. of mol.: 2 / Mutation: K129G,K129G
Source method: isolated from a genetically manipulated source
Details: FRAGMENT: PXR, RESIDUES 129-434, K129G is a cloning artifact; LINKER; SRC-1, RESIDUES 678-700
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1I2, PXR, NCOA1, BHLHE74, SRC1 / Production host: Escherichia coli (E. coli)
References: UniProt: O75469, UniProt: Q15788, histone acetyltransferase
#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-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-GRH / (2~{R})-~{N}-[4-(3-chloranylphenoxy)-3-sulfamoyl-phenyl]-2-phenyl-propanamide


Mass: 430.905 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H19ClN2O4S
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 148 / 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: 2.54 Å3/Da / Density % sol: 51.52 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 1 microliter protein at 12.1 mg/ml (in 20 millimolar Tris pH 7.8, 250 millimolar NaCl, 2.5 millimolar EDTA, 5% (v/v) glycerol, 5 mM DTT), preincubated with 10 millimolar compound 15 (from ...Details: 1 microliter protein at 12.1 mg/ml (in 20 millimolar Tris pH 7.8, 250 millimolar NaCl, 2.5 millimolar EDTA, 5% (v/v) glycerol, 5 mM DTT), preincubated with 10 millimolar compound 15 (from 200 millimolar stock in DMSO), mixed with 1 microliter of reservoir (100 mM imidazole pH 8.0, 17 % (v/v) MPD). Crystals additionally soaked in 20 millimolar compound 15 prior to data collection. cryo buffer 34% (v/v) MPD supplemented with 20 millimolar compound 15

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 1.040432 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 1, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.040432 Å / Relative weight: 1
ReflectionResolution: 2.22→45.15 Å / Num. obs: 39804 / % possible obs: 99.3 % / Redundancy: 5 % / Biso Wilson estimate: 57.6 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.065 / Net I/σ(I): 15.4
Reflection shellResolution: 2.22→2.35 Å / Redundancy: 4.9 % / Mean I/σ(I) obs: 1.7 / Num. unique obs: 6262 / CC1/2: 0.707 / Rrim(I) all: 0.847 / % possible all: 98.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0189refinement
XDSdata reduction
XDSdata scaling
REFMAC5.8.0049phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: 3HVL

3hvl


Resolution: 2.22→45.15 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.942 / SU B: 13.093 / SU ML: 0.153 / Cross valid method: THROUGHOUT / ESU R: 0.23 / ESU R Free: 0.189 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22611 1991 5 %RANDOM
Rwork0.1847 ---
obs0.18674 37812 99.34 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 69.232 Å2
Baniso -1Baniso -2Baniso -3
1--1.43 Å2-0 Å20 Å2
2--1.01 Å2-0 Å2
3---0.42 Å2
Refinement stepCycle: 1 / Resolution: 2.22→45.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4869 0 55 148 5072
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0195156
X-RAY DIFFRACTIONr_bond_other_d0.0010.024841
X-RAY DIFFRACTIONr_angle_refined_deg1.421.9726961
X-RAY DIFFRACTIONr_angle_other_deg0.973.00111239
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.45629
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.9123.633245
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.92415959
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.5421537
X-RAY DIFFRACTIONr_chiral_restr0.080.2759
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0215645
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021070
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_it4.6834.3662445
X-RAY DIFFRACTIONr_mcbond_other4.6774.3662444
X-RAY DIFFRACTIONr_mcangle_it7.1989.7753061
X-RAY DIFFRACTIONr_mcangle_other7.1989.7783062
X-RAY DIFFRACTIONr_scbond_it5.7864.8592711
X-RAY DIFFRACTIONr_scbond_other5.7864.862712
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other8.70910.6163888
X-RAY DIFFRACTIONr_long_range_B_refined12.04252.5875715
X-RAY DIFFRACTIONr_long_range_B_other12.05252.4485690
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Ens-ID: 1 / Number: 19266 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.1 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 2.219→2.277 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.335 143 -
Rwork0.293 2711 -
obs--97.97 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.1002-0.4322-0.77281.9740.48893.74610.0270.36950.0912-0.1612-0.14380.126-0.4198-0.17260.11670.05760.0182-0.00910.0853-0.00640.09518.70328.62229.909
24.11250.7602-0.17673.0285-0.26652.04580.0423-0.2182-0.30450.1668-0.012-0.10350.18510.0052-0.03030.031-0.007-0.00530.08430.00750.03854.92541.8217.948
310.6980.1265-3.47015.49170.60176.48740.04310.5465-0.40240.0267-0.05440.0770.5881-0.42130.01140.1778-0.01030.02180.2794-0.17770.26712.4112.26918.433
49.49991.26311.40885.6842-1.271312.9077-0.0861-0.207-0.6453-0.15640.2443-0.60880.69820.4529-0.15820.2701-0.02120.07860.1567-0.14660.246856.29327.039-7.36
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A138 - 434
2X-RAY DIFFRACTION2B138 - 434
3X-RAY DIFFRACTION3A442 - 461
4X-RAY DIFFRACTION4B442 - 461

+
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