[English] 日本語
Yorodumi
- PDB-5a86: Structure of pregnane X receptor in complex with a Sphingosine 1-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5a86
TitleStructure of pregnane X receptor in complex with a Sphingosine 1- Phosphate Receptor 1 Antagonist
Components
  • NUCLEAR RECEPTOR COACTIVATOR 1
  • NUCLEAR RECEPTOR SUBFAMILY 1 GROUP I MEMBER 2
KeywordsSIGNALING PROTEIN / PXR LIGAND / PXR AGONIST / CYP3A4 INDUCTION / NUCLEAR RECEPTOR
Function / homology
Function and homology information


cellular response to molecule of bacterial origin / intestinal epithelial structure maintenance / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / xenobiotic transport / hypothalamus development / steroid metabolic process / male mating behavior / progesterone receptor signaling pathway ...cellular response to molecule of bacterial origin / intestinal epithelial structure maintenance / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / xenobiotic transport / hypothalamus development / steroid metabolic process / male mating behavior / progesterone receptor signaling pathway / response to progesterone / Synthesis of bile acids and bile salts / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / cerebellum development / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / response to retinoic acid / protein-lysine-acetyltransferase activity / xenobiotic catabolic process / nuclear retinoid X receptor binding / lactation / positive regulation of neuron differentiation / estrous cycle / estrogen receptor signaling pathway / Recycling of bile acids and salts / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / histone acetyltransferase / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cellular response to hormone stimulus / intracellular receptor signaling pathway / peroxisome proliferator activated receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / positive regulation of adipose tissue development / bile acid and bile salt transport / BMAL1:CLOCK,NPAS2 activates circadian expression / regulation of cellular response to insulin stimulus / male gonad development / xenobiotic metabolic process / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Activation of gene expression by SREBF (SREBP) / SUMOylation of transcription cofactors / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / hippocampus development / nuclear estrogen receptor binding / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / Heme signaling / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / cerebral cortex development / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / mRNA transcription by RNA polymerase II / nuclear receptor activity / transcription coregulator activity / sequence-specific double-stranded DNA binding / response to estradiol / transcription regulator complex / 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 / Estrogen-dependent gene expression / DNA-binding transcription factor activity, RNA polymerase II-specific / cell differentiation / transcription coactivator activity / protein dimerization activity / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / chromatin binding / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / protein-containing complex binding / chromatin / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA-templated transcription / nucleoplasm / zinc ion binding / nucleus / cytoplasm
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 / 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-D7E / 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: 2.25 Å
AuthorsXue, Y. / Oster, L.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Identification and Optimization of Benzimidazole Sulfonamides as Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo Activity.
Authors: Hennessy, E.J. / Oza, V.B. / Adam, A. / Byth, K. / Castriotta, L. / Grewal, G. / Hamilton, G. / Kamhi, V.M. / Lewis, P. / Li, D. / Lyne, P.D. / Oster, L. / Rooney, M.T. / Saeh, J.C. / Sha, L. ...Authors: Hennessy, E.J. / Oza, V.B. / Adam, A. / Byth, K. / Castriotta, L. / Grewal, G. / Hamilton, G. / Kamhi, V.M. / Lewis, P. / Li, D. / Lyne, P.D. / Oster, L. / Rooney, M.T. / Saeh, J.C. / Sha, L. / Su, Q. / Wen, S. / Xue, Y. / Yang, B.
History
DepositionJul 13, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 21, 2015Provider: repository / Type: Initial release
Revision 1.1May 16, 2018Group: Data collection / Category: diffrn_source / Item: _diffrn_source.pdbx_synchrotron_beamline
Revision 1.2May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)77,1826
Polymers76,3184
Non-polymers8642
Water5,423301
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4030 Å2
ΔGint-34.9 kcal/mol
Surface area28480 Å2
MethodPISA
Unit cell
Length a, b, c (Å)83.670, 89.200, 106.560
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
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 / STEROID RECEPTOR COACTIVATOR 1


Mass: 36136.738 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / 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 / STEROID RECEPTOR COACTIVATOR 1


Mass: 2022.333 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: Q15788, histone acetyltransferase
#3: Chemical ChemComp-D7E / 4-chloro-N-[(1R)-1-[1-ethyl-6-(trifluoromethyl)benzimidazol-2-yl]ethyl]benzenesulfonamide


Mass: 431.860 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H17ClF3N3O2S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 301 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.61 Å3/Da / Density % sol: 52.79 % / Description: NONE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Type: ESRF / Wavelength: 0.9395
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9395 Å / Relative weight: 1
ReflectionResolution: 2.25→45.74 Å / Num. obs: 37577 / % possible obs: 98 % / Observed criterion σ(I): 0 / Redundancy: 3.8 % / Biso Wilson estimate: 49.57 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 13.9
Reflection shellResolution: 2.25→2.31 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.55 / Mean I/σ(I) obs: 2.3 / % possible all: 100

-
Processing

Software
NameVersionClassification
BUSTER2.11.6refinement
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 2.25→14.88 Å / Cor.coef. Fo:Fc: 0.9242 / Cor.coef. Fo:Fc free: 0.9175 / SU R Cruickshank DPI: 0.284 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.297 / SU Rfree Blow DPI: 0.215 / SU Rfree Cruickshank DPI: 0.213
Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. ALL ATOMS HAVE CCP4 ATOM TYPE FROM LIBRARY
RfactorNum. reflection% reflectionSelection details
Rfree0.2555 1877 5.01 %RANDOM
Rwork0.2306 ---
obs0.2319 37467 97.62 %-
Displacement parametersBiso mean: 58.84 Å2
Baniso -1Baniso -2Baniso -3
1-0.6202 Å20 Å20 Å2
2---2.5639 Å20 Å2
3---1.9436 Å2
Refine analyzeLuzzati coordinate error obs: 0.356 Å
Refinement stepCycle: LAST / Resolution: 2.25→14.88 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4724 0 56 301 5081
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0084883HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.96578HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1759SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes121HARMONIC2
X-RAY DIFFRACTIONt_gen_planes687HARMONIC5
X-RAY DIFFRACTIONt_it4883HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.23
X-RAY DIFFRACTIONt_other_torsion19.3
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion613SEMIHARMONIC5
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_contact5950SEMIHARMONIC4
LS refinement shellResolution: 2.25→2.31 Å / Total num. of bins used: 19
RfactorNum. reflection% reflection
Rfree0.3353 152 5.1 %
Rwork0.3242 2826 -
all0.3248 2978 -
obs--99.97 %

+
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