[English] 日本語
Yorodumi
- PDB-4wvd: Identification of a novel FXR ligand that regulates metabolism -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4wvd
TitleIdentification of a novel FXR ligand that regulates metabolism
Components
  • Bile acid receptor
  • Nuclear receptor corepressor 1
KeywordsTRANSCRIPTION / AF-2 helix / ligand binding pocket / three-layer helical sandwich / TRANSCRIPTION REGULATOR FXR / BAR / NR1H4 / bile acid receptor / NHR / nuclear receptor / corepressor / Transcription regulation
Function / homology
Function and homology information


Loss of MECP2 binding ability to the NCoR/SMRT complex / : / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / : / positive regulation of ammonia assimilation cycle / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid / negative regulation of interleukin-1 production ...Loss of MECP2 binding ability to the NCoR/SMRT complex / : / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / : / positive regulation of ammonia assimilation cycle / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid / negative regulation of interleukin-1 production / negative regulation of very-low-density lipoprotein particle remodeling / regulation of bile acid biosynthetic process / regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of monocyte chemotactic protein-1 production / toll-like receptor 9 signaling pathway / negative regulation of androgen receptor signaling pathway / nuclear receptor-mediated bile acid signaling pathway / bile acid nuclear receptor activity / bile acid binding / bile acid metabolic process / cellular response to fatty acid / cell-cell junction assembly / nuclear thyroid hormone receptor binding / regulation of cholesterol metabolic process / negative regulation of glycolytic process / negative regulation of JNK cascade / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of interleukin-2 production / negative regulation of fatty acid metabolic process / bile acid and bile salt transport / Notch-HLH transcription pathway / locomotor rhythm / histone deacetylase complex / positive regulation of interleukin-17 production / negative regulation of type II interferon production / negative regulation of interleukin-6 production / Synthesis of bile acids and bile salts / negative regulation of tumor necrosis factor production / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Regulation of MECP2 expression and activity / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / fatty acid homeostasis / positive regulation of insulin receptor signaling pathway / negative regulation of tumor necrosis factor-mediated signaling pathway / Nuclear signaling by ERBB4 / nuclear retinoid X receptor binding / Recycling of bile acids and salts / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / intracellular receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / spindle assembly / Notch signaling pathway / transcription repressor complex / positive regulation of adipose tissue development / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / negative regulation of miRNA transcription / intracellular glucose homeostasis / ciliary tip / cholesterol homeostasis / nuclear receptor binding / positive regulation of insulin secretion involved in cellular response to glucose stimulus / transcription coregulator binding / negative regulation of canonical NF-kappaB signal transduction / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / HDACs deacetylate histones / Heme signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / euchromatin / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / negative regulation of inflammatory response / NOTCH1 Intracellular Domain Regulates Transcription / nuclear receptor activity / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Activation of anterior HOX genes in hindbrain development during early embryogenesis / RNA polymerase II transcription regulator complex / histone deacetylase binding / HCMV Early Events / mitotic spindle / transcription corepressor activity / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / chromatin organization / cellular response to lipopolysaccharide / DNA-binding transcription activator activity, RNA polymerase II-specific / transcription by RNA polymerase II / sequence-specific DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / DNA-binding transcription factor activity, RNA polymerase II-specific / cell differentiation / signaling receptor complex / defense response to bacterium / transcription cis-regulatory region binding / nuclear speck
Similarity search - Function
N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Bile acid receptor, ligand binding domain / Thyroid hormone receptor / SANT domain profile. / SANT domain / Myb domain / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains ...N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Bile acid receptor, ligand binding domain / Thyroid hormone receptor / SANT domain profile. / SANT domain / Myb domain / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Homeobox-like domain superfamily / 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
FORMIC ACID / Chem-IVM / Nuclear receptor corepressor 1 / Bile acid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsWang, R. / Li, Y.
Funding support China, 4items
OrganizationGrant numberCountry
National Basic Research Program of China973 Program: 2012CB910104 China
National Natural Science Foundation of China81273567 China
National Natural Science Foundation of China31270776 China
Programme of Introducing Talents of Discipline to UniversitiesB12001 China
CitationJournal: Nat Commun / Year: 2013
Title: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism.
Authors: Jin, L. / Feng, X. / Rong, H. / Pan, Z. / Inaba, Y. / Qiu, L. / Zheng, W. / Lin, S. / Wang, R. / Wang, Z. / Wang, S. / Liu, H. / Li, S. / Xie, W. / Li, Y.
History
DepositionNov 5, 2014Deposition site: RCSB / Processing site: PDBJ
SupersessionFeb 11, 2015ID: 4II6
Revision 1.0Feb 11, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2015Group: Data collection
Revision 1.2Sep 27, 2017Group: Data collection / Derived calculations / Category: diffrn_detector / pdbx_struct_oper_list
Item: _diffrn_detector.detector / _pdbx_struct_oper_list.symmetry_operation
Revision 1.3Mar 20, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name
Revision 1.4Mar 12, 2025Group: Database references / Structure summary / Category: pdbx_database_related / pdbx_entry_details / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Nuclear receptor corepressor 1
A: Bile acid receptor
D: Nuclear receptor corepressor 1
B: Bile acid receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,05914
Polymers52,9414
Non-polymers2,11810
Water19811
1
C: Nuclear receptor corepressor 1
A: Bile acid receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,5307
Polymers26,4702
Non-polymers1,0595
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1150 Å2
ΔGint-11 kcal/mol
Surface area12470 Å2
MethodPISA
2
D: Nuclear receptor corepressor 1
B: Bile acid receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,5307
Polymers26,4702
Non-polymers1,0595
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1090 Å2
ΔGint-11 kcal/mol
Surface area12180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.008, 161.759, 169.018
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number24
Space group name H-MI212121
Components on special symmetry positions
IDModelComponents
11A-601-

HOH

Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2given(-0.998958, -0.037084, -0.026618), (0.032136, -0.157183, -0.987046), (0.03242, -0.986873, 0.158211)-14.3448, -40.819679, -34.91283
3given(1), (1), (1)
4given(-0.993996, -0.098282, -0.048084), (0.061121, -0.134271, -0.989058), (0.090751, -0.986059, 0.139472)-14.90824, -40.129929, -33.526199
Detailsbiological unit is a dimer. There are 2 biological units in the asymmetric unit (chains A & B and chains C & D)

-
Components

#1: Protein/peptide Nuclear receptor corepressor 1 / N-CoR1


Mass: 1866.189 Da / Num. of mol.: 2 / Fragment: UNP residues 2259-2275 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: O75376
#2: Protein Bile acid receptor / Farnesoid X-activated receptor / Farnesol receptor HRR-1 / Nuclear receptor subfamily 1 group H ...Farnesoid X-activated receptor / Farnesol receptor HRR-1 / Nuclear receptor subfamily 1 group H member 4 / Retinoid X receptor-interacting protein 14 / RXR-interacting protein 14


Mass: 24604.262 Da / Num. of mol.: 2 / Fragment: Ligand Binding Domain, UNP residues 244-454
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H4, BAR, FXR, HRR1, RIP14 / Plasmid: pET24 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q96RI1
#3: Chemical
ChemComp-FMT / FORMIC ACID


Mass: 46.025 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: CH2O2
#4: Chemical ChemComp-IVM / (2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-[(2S)-butan-2-yl]-20,20b-dihydroxy-5',6,8,19-tetramethyl-17 -oxo-3',4',5',6,6',10,11,14,15,17,17a,20,20a,20b-tetradecahydro-2H,7H-spiro[11,15-methanofuro[4,3,2-pq][2,6]benzodioxacy clooctadecine-13,2'-pyran]-7-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranosyl)-3-O-methyl-alpha-L-arabino-hexopyranoside / 22,23-DIHYDROAVERMECTIN B1A / IVERMECTIN


Mass: 875.093 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C48H74O14 / Comment: medication, antiparasitic*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 11 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationN
Sequence detailsTHIS SEQUENCE CORRESPONDS TO THE ISOFORM 4 FOUND IN UNP 075376.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.51 Å3/Da / Density % sol: 64.98 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 50mM HEPES pH7.0, 3.5M sodium formate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 1.005 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 9, 2012
RadiationMonochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.005 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 20898 / % possible obs: 64.1 % / Redundancy: 7.5 % / Rmerge(I) obs: 0.104 / Net I/σ(I): 10.4
Reflection shellResolution: 2.3→2.34 Å / Redundancy: 1 % / Rmerge(I) obs: 0.77

-
Processing

Software
NameVersionClassification
REFMAC5.8.0073refinement
PDB_EXTRACT3.15data extraction
HKL-2000data reduction
HKL-2000data scaling
Cootmodel building
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9→50 Å / Cor.coef. Fo:Fc: 0.878 / Cor.coef. Fo:Fc free: 0.872 / SU B: 17.293 / SU ML: 0.345 / Cross valid method: THROUGHOUT / ESU R: 1.28 / ESU R Free: 0.427 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.30221 819 5 %RANDOM
Rwork0.27741 ---
obs0.27872 15531 98.27 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 75.502 Å2
Baniso -1Baniso -2Baniso -3
1-0.02 Å20 Å20 Å2
2---0.12 Å2-0 Å2
3---0.1 Å2
Refinement stepCycle: LAST / Resolution: 2.9→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3484 0 148 11 3643
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0193562
X-RAY DIFFRACTIONr_bond_other_d0.0060.023334
X-RAY DIFFRACTIONr_angle_refined_deg1.731.9694809
X-RAY DIFFRACTIONr_angle_other_deg1.04337652
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.3785445
X-RAY DIFFRACTIONr_dihedral_angle_2_deg42.28525.247162
X-RAY DIFFRACTIONr_dihedral_angle_3_deg23.30415607
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.9871514
X-RAY DIFFRACTIONr_chiral_restr0.0880.2556
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0214044
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02796
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_it5.9667.8241798
X-RAY DIFFRACTIONr_mcbond_other5.9647.821799
X-RAY DIFFRACTIONr_mcangle_it8.94611.7242237
X-RAY DIFFRACTIONr_mcangle_other8.94611.7252238
X-RAY DIFFRACTIONr_scbond_it8.6858.0881762
X-RAY DIFFRACTIONr_scbond_other8.6928.0971749
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other11.83911.9612572
X-RAY DIFFRACTIONr_long_range_B_refined13.61263.1924220
X-RAY DIFFRACTIONr_long_range_B_other13.61863.1994215
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.9→2.975 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.352 53 -
Rwork0.281 1048 -
obs--90.62 %

+
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