[English] 日本語
Yorodumi
- PDB-3omk: Crystal structure of human FXR in complex with (2S)-2-[2-(4-chlor... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3omk
TitleCrystal structure of human FXR in complex with (2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexyl-N-(2-methylphenyl)ethanamide
Components
  • Bile acid receptor
  • peptide of Nuclear receptor coactivator 1
KeywordsHORMONE RECEPTOR / NUCLEAR RECEPTOR / CHOLESTEROL / BILE ACID / DNA-BINDING / NUCLEUS / RECEPTOR / TRANSCRIPTION / LIGAND BINDING DOMAIN TRANSCRIPTION REGULATION / COACTIVATOR / FXR ALTERNATIVE SPLICING
Function / homology
Function and homology information


regulation of urea metabolic process / intracellular bile acid receptor signaling pathway / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / positive regulation of glutamate metabolic process / positive regulation of ammonia assimilation cycle / bile acid receptor activity / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid ...regulation of urea metabolic process / intracellular bile acid receptor signaling pathway / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / positive regulation of glutamate metabolic process / positive regulation of ammonia assimilation cycle / bile acid receptor activity / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid / negative regulation of very-low-density lipoprotein particle remodeling / negative regulation of interleukin-1 production / regulation of bile acid biosynthetic process / regulation of insulin secretion involved in cellular response to glucose stimulus / cellular response to organonitrogen compound / toll-like receptor 9 signaling pathway / negative regulation of monocyte chemotactic protein-1 production / intracellular receptor signaling pathway / bile acid metabolic process / nitrogen catabolite activation of transcription from RNA polymerase II promoter / labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / cell-cell junction assembly / positive regulation of female receptivity / regulation of cholesterol metabolic process / bile acid binding / bile acid signaling pathway / negative regulation of interleukin-2 production / cellular response to fatty acid / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / positive regulation of interleukin-17 production / positive regulation of insulin secretion involved in cellular response to glucose stimulus / intracellular glucose homeostasis / negative regulation of interleukin-6 production / estrous cycle / negative regulation of type II interferon production / cellular response to Thyroglobulin triiodothyronine / negative regulation of tumor necrosis factor production / Synthesis of bile acids and bile salts / negative regulation of tumor necrosis factor-mediated signaling pathway / fatty acid homeostasis / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / response to retinoic acid / negative regulation of canonical NF-kappaB signal transduction / positive regulation of insulin receptor signaling pathway / histone acetyltransferase activity / Recycling of bile acids and salts / regulation of cellular response to insulin stimulus / histone acetyltransferase / Notch signaling pathway / cellular response to hormone stimulus / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / positive regulation of neuron differentiation / RORA activates gene expression / lactation / Regulation of lipid metabolism by PPARalpha / cerebellum development / cholesterol homeostasis / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / nuclear receptor coactivator activity / Activation of gene expression by SREBF (SREBP) / response to progesterone / nuclear estrogen receptor binding / transcription coregulator binding / nuclear receptor binding / hippocampus development / RNA polymerase II transcription regulatory region sequence-specific DNA binding / euchromatin / SUMOylation of intracellular receptors / Heme signaling / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / negative regulation of inflammatory response / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / male gonad development / nuclear receptor activity / Circadian Clock / response to estradiol / HATs acetylate histones / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / cellular response to lipopolysaccharide / transcription regulator complex / sequence-specific DNA binding / transcription by RNA polymerase II / cell differentiation
Similarity search - Function
Bile acid receptor, ligand binding domain / Thyroid hormone receptor / 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 ...Bile acid receptor, ligand binding domain / Thyroid hormone receptor / 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-OMK / Nuclear receptor coactivator 1 / Bile acid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsRudolph, M.G.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2011
Title: Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties
Authors: Richter, H.G.F. / Benson, G.M. / Bleicher, K.H. / Blum, D. / Chaput, E. / Clemann, N. / Feng, S. / Gardes, C. / Grether, U. / Hartman, P. / Kuhn, B. / Martin, R.E. / Plancher, J.M. / ...Authors: Richter, H.G.F. / Benson, G.M. / Bleicher, K.H. / Blum, D. / Chaput, E. / Clemann, N. / Feng, S. / Gardes, C. / Grether, U. / Hartman, P. / Kuhn, B. / Martin, R.E. / Plancher, J.M. / Rudolph, M.G. / Schuler, F. / Taylor, S.
History
DepositionAug 27, 2010Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jan 19, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Feb 26, 2014Group: Database references
Revision 1.3Nov 8, 2017Group: Refinement description / Category: software
Revision 1.4Mar 20, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bile acid receptor
B: peptide of Nuclear receptor coactivator 1
C: Bile acid receptor
D: peptide of Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,7686
Polymers57,7804
Non-polymers9882
Water3,675204
1
A: Bile acid receptor
B: peptide of Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,3843
Polymers28,8902
Non-polymers4941
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1170 Å2
ΔGint-7 kcal/mol
Surface area12560 Å2
MethodPISA
2
C: Bile acid receptor
D: peptide of Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,3843
Polymers28,8902
Non-polymers4941
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1160 Å2
ΔGint-6 kcal/mol
Surface area12420 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.320, 84.710, 190.010
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Bile acid receptor / fxr / Farnesoid X-activated receptor / Farnesol receptor HRR-1 / Nuclear receptor subfamily 1 group ...fxr / 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: 27100.191 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 258-486 / Mutation: E281A, E354A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H4, HCG_20893 / Plasmid: PET28A / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q96RI1
#2: Protein/peptide peptide of 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: 1790.026 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 744-757 / Source method: obtained synthetically / Details: THIS SEQUENCE OCCURS NATURALLY IN HUMANS / References: UniProt: Q15788
#3: Chemical ChemComp-OMK / (2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexyl-N-(2-methylphenyl)ethanamide


Mass: 493.975 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C28H26ClF2N3O
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 204 / 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: 2.52 Å3/Da / Density % sol: 51.16 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.1M Bis-Tris pH 6.5, 25% PEG 3350, VAPOR DIFFUSION, SITTING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 2, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.9→38.68 Å / Num. obs: 46039 / % possible obs: 99.2 % / Observed criterion σ(I): 1 / Redundancy: 7.07 % / Biso Wilson estimate: 34.48 Å2 / Rmerge(I) obs: 0.0764 / Rsym value: 0.0764 / Net I/σ(I): 12.45
Reflection shellResolution: 1.9→2 Å / Redundancy: 5.55 % / Rmerge(I) obs: 0.6555 / Mean I/σ(I) obs: 1.89 / Rsym value: 0.6555 / % possible all: 95.4

-
Processing

Software
NameVersionClassification
PHASERphasing
BUSTER2.9.5refinement
XDS(VERSION June 12data reduction
SADABSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: INHOUSE

Resolution: 1.9→38.68 Å / Cor.coef. Fo:Fc: 0.9515 / Cor.coef. Fo:Fc free: 0.9311 / SU R Cruickshank DPI: 0.148 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.15 / SU Rfree Blow DPI: 0.14 / SU Rfree Cruickshank DPI: 0.14
RfactorNum. reflection% reflectionSelection details
Rfree0.2449 2305 5.01 %RANDOM
Rwork0.2038 ---
obs0.2059 45992 99.19 %-
Displacement parametersBiso mean: 42.92 Å2
Baniso -1Baniso -2Baniso -3
1-4.1206 Å20 Å20 Å2
2---6.9701 Å20 Å2
3---2.8496 Å2
Refine analyzeLuzzati coordinate error obs: 0.301 Å
Refinement stepCycle: LAST / Resolution: 1.9→38.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3962 0 70 204 4236
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1492SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes118HARMONIC2
X-RAY DIFFRACTIONt_gen_planes579HARMONIC5
X-RAY DIFFRACTIONt_it4147HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion532SEMIHARMONIC5
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_contact4946SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4147HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg5610HARMONIC21.06
X-RAY DIFFRACTIONt_omega_torsion2.34
X-RAY DIFFRACTIONt_other_torsion21.53
LS refinement shellResolution: 1.9→1.95 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.4257 148 4.76 %
Rwork0.4124 2961 -
all0.4131 3109 -
obs--99.19 %

+
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