[English] 日本語
Yorodumi
- PDB-3fc6: hRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3fc6
TitlehRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875
Components
  • Nr1h3 protein
  • Retinoic acid receptor RXR-alpha
KeywordsTRANSCRIPTION / Liver X receptor / nuclear hormone receptors / agonists / epoxycholesterol / DNA-binding / Host-virus interaction / Metal-binding / Nucleus / Polymorphism / Receptor / Transcription regulation / Ubl conjugation / Zinc / Zinc-finger
Function / homology
Function and homology information


regulation of secretion of lysosomal enzymes / regulation of pancreatic juice secretion / negative regulation of secretion of lysosomal enzymes / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / sterol response element binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / SUMOylation of intracellular receptors / negative regulation of pancreatic juice secretion / negative regulation of macrophage activation / Nuclear Receptor transcription pathway ...regulation of secretion of lysosomal enzymes / regulation of pancreatic juice secretion / negative regulation of secretion of lysosomal enzymes / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / sterol response element binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / SUMOylation of intracellular receptors / negative regulation of pancreatic juice secretion / negative regulation of macrophage activation / Nuclear Receptor transcription pathway / phosphatidylcholine acyl-chain remodeling / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / sterol homeostasis / regulation of lipid storage / VLDLR internalisation and degradation / positive regulation of triglyceride biosynthetic process / positive regulation of toll-like receptor 4 signaling pathway / retinoic acid-responsive element binding / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / positive regulation of thyroid hormone receptor signaling pathway / regulation of fatty acid metabolic process / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / positive regulation of fatty acid biosynthetic process / Carnitine shuttle / negative regulation of lipid transport / retinoic acid binding / bile acid metabolic process / TGFBR3 expression / positive regulation of vitamin D receptor signaling pathway / nuclear vitamin D receptor binding / apoptotic cell clearance / negative regulation of cold-induced thermogenesis / Signaling by Retinoic Acid / positive regulation of cholesterol transport / triglyceride homeostasis / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / DNA binding domain binding / positive regulation of lipid metabolic process / negative regulation of cholesterol storage / LBD domain binding / positive regulation of lipoprotein transport / lipid homeostasis / nuclear steroid receptor activity / Synthesis of bile acids and bile salts / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / positive regulation of cholesterol efflux / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / monocyte differentiation / response to retinoic acid / positive regulation of bone mineralization / cellular response to low-density lipoprotein particle stimulus / positive regulation of lipid biosynthetic process / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / Recycling of bile acids and salts / retinoic acid receptor signaling pathway / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / intracellular receptor signaling pathway / negative regulation of proteolysis / Regulation of lipid metabolism by PPARalpha / cell maturation / peptide binding / peroxisome proliferator activated receptor signaling pathway / response to progesterone / hormone-mediated signaling pathway / BMAL1:CLOCK,NPAS2 activates circadian expression / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Activation of gene expression by SREBF (SREBP) / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / cholesterol homeostasis / transcription coregulator binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / lipid metabolic process / Heme signaling / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / chromatin DNA binding / mRNA transcription by RNA polymerase II / negative regulation of inflammatory response / nuclear receptor activity / Activation of anterior HOX genes in hindbrain development during early embryogenesis / RNA polymerase II transcription regulator complex / Transcriptional regulation of granulopoiesis / fatty acid biosynthetic process / sequence-specific double-stranded DNA binding / nervous system development / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / cellular response to lipopolysaccharide / double-stranded DNA binding / DNA-binding transcription activator activity, RNA polymerase II-specific / transcription regulator complex / sequence-specific DNA binding
Similarity search - Function
Liver X receptor / Nuclear/hormone receptor activator site AF-1 / Nuclear/hormone receptor activator site AF-1 / Retinoid X receptor/HNF4 / : / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. ...Liver X receptor / Nuclear/hormone receptor activator site AF-1 / Nuclear/hormone receptor activator site AF-1 / Retinoid X receptor/HNF4 / : / : / Retinoid X Receptor / Retinoid X Receptor / 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-LX2 / RETINOIC ACID / Retinoic acid receptor RXR-alpha / Nr1h3 protein / Oxysterols receptor LXR-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.063 Å
AuthorsWashburn, D.G. / Hoang, T.H. / Campobasso, N. / Smallwood, A. / Parks, D.J. / Webb, C.L. / Frank, K. / Nord, M. / Duraiswami, C. / Evans, C. ...Washburn, D.G. / Hoang, T.H. / Campobasso, N. / Smallwood, A. / Parks, D.J. / Webb, C.L. / Frank, K. / Nord, M. / Duraiswami, C. / Evans, C. / Jaye, M. / Thompson, S.K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2009
Title: Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.
Authors: Washburn, D.G. / Hoang, T.H. / Campobasso, N. / Smallwood, A. / Parks, D.J. / Webb, C.L. / Frank, K.A. / Nord, M. / Duraiswami, C. / Evans, C. / Jaye, M. / Thompson, S.K.
History
DepositionNov 21, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 10, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Dec 27, 2023Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Retinoic acid receptor RXR-alpha
B: Nr1h3 protein
C: Retinoic acid receptor RXR-alpha
D: Nr1h3 protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)117,3088
Polymers115,4654
Non-polymers1,8434
Water4,125229
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area11230 Å2
ΔGint-59 kcal/mol
Surface area37420 Å2
MethodPISA
Unit cell
Length a, b, c (Å)122.162, 90.029, 101.642
Angle α, β, γ (deg.)90.00, 111.92, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Retinoic acid receptor RXR-alpha / Retinoid X receptor alpha / Nuclear receptor subfamily 2 group B member 1


Mass: 27114.465 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P19793
#2: Protein Nr1h3 protein / Putative uncharacterized protein / Nuclear receptor subfamily 1 group H member 3 / Nuclear receptor ...Putative uncharacterized protein / Nuclear receptor subfamily 1 group H member 3 / Nuclear receptor subfamily 1 / group H / member 3 / Nuclear receptor subfamily 1 / group H / member 3 / isoform CRA_a


Mass: 30618.035 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q91X41, UniProt: Q9Z0Y9*PLUS
#3: Chemical ChemComp-REA / RETINOIC ACID


Mass: 300.435 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H28O2
#4: Chemical ChemComp-LX2 / [4-(3-{[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino}propoxy)-1H-indol-1-yl]acetic acid


Mass: 621.088 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C35H32ClF3N2O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 229 / 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: 2.25 Å3/Da / Density % sol: 45.22 %

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Aug 23, 2003
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.06→44.2 Å / Num. all: 62907 / Num. obs: 58748 / % possible obs: 93.4 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 3.7 % / Biso Wilson estimate: 26.1 Å2 / Rmerge(I) obs: 0.082 / Rsym value: 0.082 / Net I/σ(I): 7.9
Reflection shellResolution: 2.06→2.13 Å / Rmerge(I) obs: 0.376 / Mean I/σ(I) obs: 2.2 / % possible all: 71.3

-
Processing

Software
NameVersionClassification
HKL-2000data collection
MLPHAREphasing
PHENIX(phenix.refine)refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.063→44.2 Å / SU ML: 0.34 / σ(F): 0.03 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2501 2820 5.07 %
Rwork0.1987 --
obs0.2014 55572 88.26 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 31.174 Å2 / ksol: 0.342 e/Å3
Refinement stepCycle: LAST / Resolution: 2.063→44.2 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7150 0 132 229 7511
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.063-2.09810.3673810.26751647X-RAY DIFFRACTION55
2.0981-2.13630.33581140.2661953X-RAY DIFFRACTION66
2.1363-2.17730.32851260.24962150X-RAY DIFFRACTION72
2.1773-2.22180.29961100.23442273X-RAY DIFFRACTION76
2.2218-2.27010.30371260.21672356X-RAY DIFFRACTION80
2.2701-2.32290.28091450.20662529X-RAY DIFFRACTION85
2.3229-2.3810.26931470.20022631X-RAY DIFFRACTION89
2.381-2.44540.2391430.19942685X-RAY DIFFRACTION90
2.4454-2.51730.23351400.20952736X-RAY DIFFRACTION92
2.5173-2.59850.28671410.21682750X-RAY DIFFRACTION92
2.5985-2.69140.27111490.21692770X-RAY DIFFRACTION93
2.6914-2.79920.25751590.22232807X-RAY DIFFRACTION94
2.7992-2.92650.29331360.20762863X-RAY DIFFRACTION95
2.9265-3.08080.26931500.21642889X-RAY DIFFRACTION96
3.0808-3.27370.24011670.21242879X-RAY DIFFRACTION97
3.2737-3.52640.24581340.19792942X-RAY DIFFRACTION98
3.5264-3.88110.2041830.17412928X-RAY DIFFRACTION98
3.8811-4.44230.21181610.15112960X-RAY DIFFRACTION99
4.4423-5.5950.2071570.16642982X-RAY DIFFRACTION99
5.595-44.23130.21641510.1763022X-RAY DIFFRACTION98

+
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