[English] 日本語
Yorodumi
- PDB-7trb: CRYSTAL STRUCTURE OF FARNESOID X-ACTIVATED RECEPTOR COMPLEXED WIT... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7trb
TitleCRYSTAL STRUCTURE OF FARNESOID X-ACTIVATED RECEPTOR COMPLEXED WITH COMPOUND-32 AKA (1S,3S)-N-({4-[5-(2-FLUOROPR OPAN-2-YL)-1,2,4-OXADIAZOL-3-YL]BICYCLO[2.2.2]OCTAN-1-YL}M ETHYL)-3-HYDROXY-N-[4'-(2-HYDROXYPROPAN-2-YL)-[1,1'-BIPHEN YL]-3-YL]-3-(TRIFLUOROMETHYL)CYCLOBUTANE-1-CARBOXAMIDE
Components
  • Bile acid receptor
  • co-activatorCoactivator (genetics)
KeywordsNUCLEAR PROTEIN / NHR / FXR
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 / bile acid binding / cell-cell junction assembly / bile acid signaling pathway / negative regulation of interleukin-2 production / cellular response to fatty acid / regulation of cholesterol metabolic process / positive regulation of interleukin-17 production / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of interleukin-6 production / negative regulation of type II interferon production / 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 / negative regulation of canonical NF-kappaB signal transduction / positive regulation of insulin receptor signaling pathway / Recycling of bile acids and salts / Notch signaling pathway / positive regulation of adipose tissue development / cholesterol homeostasis / transcription coregulator binding / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / euchromatin / PPARA activates gene expression / negative regulation of inflammatory response / Nuclear Receptor transcription pathway / nuclear receptor activity / DNA-binding transcription activator activity, RNA polymerase II-specific / cellular response to lipopolysaccharide / sequence-specific DNA binding / transcription by RNA polymerase II / cell differentiation / receptor complex / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / defense response to bacterium / inflammatory response / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / innate immune response / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm
Similarity search - Function
Bile acid receptor, ligand binding domain / Thyroid hormone 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 ...Bile acid receptor, ligand binding domain / Thyroid hormone 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
Similarity search - Domain/homology
Chem-IUS / Bile acid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsKhan, J.A. / Ruzanov, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis.
Authors: Nara, S.J. / Jogi, S. / Cheruku, S. / Kandhasamy, S. / Jaipuri, F. / Kathi, P.K. / Reddy, S. / Sarodaya, S. / Cook, E.M. / Wang, T. / Sitkoff, D. / Rossi, K.A. / Ruzanov, M. / Kiefer, S.E. / ...Authors: Nara, S.J. / Jogi, S. / Cheruku, S. / Kandhasamy, S. / Jaipuri, F. / Kathi, P.K. / Reddy, S. / Sarodaya, S. / Cook, E.M. / Wang, T. / Sitkoff, D. / Rossi, K.A. / Ruzanov, M. / Kiefer, S.E. / Khan, J.A. / Gao, M. / Reddy, S. / Sivaprasad Lvj, S. / Sane, R. / Mosure, K. / Zhuo, X. / Cao, G.G. / Ziegler, M. / Azzara, A. / Krupinski, J. / Soars, M.G. / Ellsworth, B.A. / Wacker, D.A.
History
DepositionJan 28, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 29, 2022Provider: repository / Type: Initial release
Revision 1.1Jul 27, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bile acid receptor
B: Bile acid receptor
C: co-activator
D: co-activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,2626
Polymers61,9754
Non-polymers1,2872
Water23413
1
A: Bile acid receptor
C: co-activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6313
Polymers30,9872
Non-polymers6441
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1060 Å2
ΔGint-6 kcal/mol
Surface area11310 Å2
MethodPISA
2
B: Bile acid receptor
D: co-activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6313
Polymers30,9872
Non-polymers6441
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1070 Å2
ΔGint-8 kcal/mol
Surface area11740 Å2
MethodPISA
Unit cell
Length a, b, c (Å)104.710, 119.260, 36.710
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

-
Components

#1: 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: 29197.453 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H4, BAR, FXR, HRR1, RIP14 / Plasmid: pET15b / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q96RI1
#2: Protein/peptide co-activator / Coactivator (genetics)


Mass: 1790.026 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#3: Chemical ChemComp-IUS / (1s,3s)-N-({4-[5-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-3-yl]bicyclo[2.2.2]octan-1-yl}methyl)-3-hydroxy-N-[4'-(2-hydroxypropan-2-yl)[1,1'-biphenyl]-3-yl]-3-(trifluoromethyl)cyclobutane-1-carboxamide


Mass: 643.711 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C35H41F4N3O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 13 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.85 Å3/Da / Density % sol: 33.49 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 28.5% PEG2000MME 0.1M NaAc trihydrate 0.1M MES pH 6.5 10mM BME
PH range: 6.5?

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 7, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→78.69 Å / Num. obs: 17574 / % possible obs: 92.1 % / Redundancy: 5.8 % / Biso Wilson estimate: 56.18 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 10.1
Reflection shellResolution: 2.19→2.37 Å / Redundancy: 4.2 % / Rmerge(I) obs: 1.037 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 880 / % possible all: 50.2

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
PDB_EXTRACT3.27data extraction
MOSFLMdata reduction
autoPROCdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3RUT

3rut


Resolution: 2.15→26.97 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.926 / SU R Cruickshank DPI: 0.663 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.595 / SU Rfree Blow DPI: 0.281 / SU Rfree Cruickshank DPI: 0.287
RfactorNum. reflection% reflectionSelection details
Rfree0.256 854 4.86 %RANDOM
Rwork0.214 ---
obs0.216 17570 68.4 %-
Displacement parametersBiso max: 161.06 Å2 / Biso mean: 66.4 Å2 / Biso min: 26.58 Å2
Baniso -1Baniso -2Baniso -3
1--1.7637 Å20 Å20 Å2
2--0.5834 Å20 Å2
3---1.1803 Å2
Refine analyzeLuzzati coordinate error obs: 0.36 Å
Refinement stepCycle: final / Resolution: 2.15→26.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3607 0 92 13 3712
Biso mean--95.21 50.95 -
Num. residues----468
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1312SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes696HARMONIC5
X-RAY DIFFRACTIONt_it3891HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion509SEMIHARMONIC5
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_contact4460SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3891HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg5388HARMONIC21.08
X-RAY DIFFRACTIONt_omega_torsion2.29
X-RAY DIFFRACTIONt_other_torsion20.27
LS refinement shellResolution: 2.15→2.32 Å / Rfactor Rfree error: 0 / Total num. of bins used: 42
RfactorNum. reflection% reflection
Rfree0.2421 33 7.88 %
Rwork0.2159 386 -
all0.2181 419 -
obs--8.32 %

+
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