[English] 日本語
Yorodumi
- PDB-5avi: Crystal structure of LXRalpha in complex with tert-butyl benzoate... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5avi
TitleCrystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 4
Components
  • Nuclear receptor coactivator 1
  • Oxysterols receptor LXR-alpha
KeywordsTRANSCRIPTION / agonist / complex
Function / homology
Function and homology information


negative regulation of secretion of lysosomal enzymes / sterol response element binding / negative regulation of macrophage activation / negative regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / sterol homeostasis / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of lipoprotein lipase activity ...negative regulation of secretion of lysosomal enzymes / sterol response element binding / negative regulation of macrophage activation / negative regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / sterol homeostasis / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of lipoprotein lipase activity / positive regulation of triglyceride biosynthetic process / positive regulation of transporter activity / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / positive regulation of fatty acid biosynthetic process / negative regulation of lipid transport / labyrinthine layer morphogenesis / regulation of thyroid hormone receptor signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / triglyceride homeostasis / positive regulation of female receptivity / apoptotic cell clearance / positive regulation of cholesterol transport / negative regulation of cold-induced thermogenesis / cholesterol binding / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of type II interferon-mediated signaling pathway / negative regulation of cholesterol storage / lipid homeostasis / negative regulation of macrophage derived foam cell differentiation / cellular response to Thyroglobulin triiodothyronine / Synthesis of bile acids and bile salts / positive regulation of cholesterol efflux / estrous cycle / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / progesterone receptor signaling pathway / nuclear retinoid X receptor binding / positive regulation of lipid biosynthetic process / response to retinoic acid / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / histone acetyltransferase activity / Recycling of bile acids and salts / histone acetyltransferase / cellular response to hormone stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / estrogen receptor signaling pathway / positive regulation of adipose tissue development / RORA activates gene expression / peroxisome proliferator activated receptor signaling pathway / lactation / positive regulation of neuron differentiation / positive regulation of protein metabolic process / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / regulation of cellular response to insulin stimulus / VLDLR internalisation and degradation / cerebellum development / BMAL1:CLOCK,NPAS2 activates circadian gene expression / Activation of gene expression by SREBF (SREBP) / SUMOylation of transcription cofactors / : / cholesterol homeostasis / response to progesterone / nuclear receptor binding / negative regulation of proteolysis / nuclear estrogen receptor binding / hippocampus development / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / Heme signaling / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / regulation of circadian rhythm / Cytoprotection by HMOX1 / chromatin DNA binding / cerebral cortex development / negative regulation of inflammatory response / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / male gonad development / Circadian Clock / response to estradiol / HATs acetylate histones / cellular response to lipopolysaccharide / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / transcription coactivator activity / cell differentiation / receptor complex / transcription cis-regulatory region binding
Similarity search - Function
Liver X 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 ...Liver X 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 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 / 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-4KM / Oxysterols receptor LXR-alpha / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.7 Å
AuthorsMatsui, Y. / Hanzawa, H. / Tamaki, K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2015
Title: Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists
Authors: Matsui, Y. / Yamaguchi, T. / Yamazaki, T. / Yoshida, M. / Arai, M. / Terasaka, N. / Honzumi, S. / Wakabayashi, K. / Hayashi, S. / Nakai, D. / Hanzawa, H. / Tamaki, K.
History
DepositionJun 16, 2015Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 26, 2015Provider: repository / Type: Initial release
Revision 1.1Nov 8, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Source and taxonomy
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / entity_src_gen / pdbx_entity_src_syn / pdbx_initial_refinement_model / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list / struct_ncs_dom_lim
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _pdbx_entity_src_syn.pdbx_alt_source_flag / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_assembly_prop.type / _pdbx_struct_assembly_prop.value / _pdbx_struct_oper_list.symmetry_operation / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Oxysterols receptor LXR-alpha
B: Nuclear receptor coactivator 1
C: Oxysterols receptor LXR-alpha
D: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,1926
Polymers71,3454
Non-polymers8472
Water1,29772
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5170 Å2
ΔGint-35 kcal/mol
Surface area22990 Å2
MethodPISA
Unit cell
Length a, b, c (Å)124.356, 124.356, 91.916
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number90
Space group name H-MP4212
Components on special symmetry positions
IDModelComponents
11A-624-

HOH

21C-624-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21C
12B
22D

NCS domain segments:

Refine code: 5

Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
111LEULEUGLNGLNAA206 - 22142 - 57
211LEULEUGLNGLNCC206 - 22142 - 57
121ARGARGTHRTHRAA253 - 31489 - 150
221ARGARGTHRTHRCC253 - 31489 - 150
131TYRTYRHISHISAA321 - 446157 - 282
231TYRTYRHISHISCC321 - 446157 - 282
112ARGARGGLUGLUBB686 - 69611 - 21
212ARGARGGLUGLUDD686 - 69611 - 21

NCS ensembles :
ID
1
2

-
Components

#1: Protein Oxysterols receptor LXR-alpha / Liver X receptor alpha / Nuclear receptor subfamily 1 group H member 3


Mass: 32866.391 Da / Num. of mol.: 2 / Fragment: ligand binding domain, UNP residues 182-447
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H3, LXRA / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q13133
#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


Mass: 2806.163 Da / Num. of mol.: 2 / Fragment: UNP residues 676-700 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15788, histone acetyltransferase
#3: Chemical ChemComp-4KM / tert-butyl 2-[[4-[ethanoyl(methyl)amino]phenoxy]methyl]-5-(trifluoromethyl)benzoate


Mass: 423.425 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H24F3NO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 72 / 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: 2.49 Å3/Da / Density % sol: 50.61 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: PEG2000MME, ammonium sulfate, Tris-HCl

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.54 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Jul 17, 2003
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.7→40 Å / Num. obs: 20300 / % possible obs: 99.5 % / Redundancy: 15.2 % / Rmerge(I) obs: 0.084 / Χ2: 1.263 / Net I/av σ(I): 18.87 / Net I/σ(I): 14.6 / Num. measured all: 122495
Reflection shell
Resolution (Å)Rmerge(I) obsNum. unique allΧ2Diffraction-IDRejects% possible all
2.7-2.80.30319821.0761099.5
2.8-2.910.24119831.1051099.7
2.91-3.040.23120011.1241099.9
3.04-3.20.17720151.16710100
3.2-3.40.14420071.20610100
3.4-3.660.09720381.32710100
3.66-4.030.07220181.28310100
4.03-4.620.05220531.46410100
4.62-5.810.0520651.3641099.6
5.81-400.03421381.4041096.4

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMAC5.7.0029refinement
DENZOdata collection
SCALEPACKdata scaling
CNSphasing
PDB_EXTRACT3.15data extraction
DENZOdata reduction
SCALEPACKdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1DB1

1db1


Resolution: 2.7→20 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.879 / SU B: 27.191 / SU ML: 0.274 / Cross valid method: THROUGHOUT / ESU R: 1.006 / ESU R Free: 0.363 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.27398 2013 9.9 %RANDOM
Rwork0.24388 ---
obs0.24695 18276 99.46 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 40.538 Å2
Baniso -1Baniso -2Baniso -3
1-0.17 Å2-0 Å2-0 Å2
2--0.17 Å2-0 Å2
3----0.33 Å2
Refinement stepCycle: LAST / Resolution: 2.7→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3965 0 60 72 4097
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0194109
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.6671.9765558
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4635476
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.54623.707205
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.12415735
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.8891534
X-RAY DIFFRACTIONr_chiral_restr0.0950.2618
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0213136
X-RAY DIFFRACTIONr_gen_planes_other
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_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION

Ens-IDDom-IDAuth asym-IDNumberTypeRms dev position (Å)Weight position
11A816medium positional0.080.5
22B44medium positional0.080.5
11C836loose positional0.335
22D57loose positional0.365
11A816medium thermal0.692
22B44medium thermal0.562
11C836loose thermal0.8310
22D57loose thermal0.6210
LS refinement shellResolution: 2.7→2.769 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.356 141 -
Rwork0.302 1307 -
obs--99.52 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.54130.0813-0.53221.5706-0.61042.6993-0.04540.1797-0.0818-0.14420.10350.1591-0.0957-0.4524-0.05810.03940.0147-0.02020.1163-0.01910.0414146.82818.400769.1944
21.75040.0953-0.26272.1108-1.20972.80510.0988-0.26330.18330.4207-0.01-0.0169-0.6323-0.0531-0.08890.1995-0.0205-0.00090.0642-0.01460.0319166.492738.657568.5972
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A204 - 446
2X-RAY DIFFRACTION1B682 - 696
3X-RAY DIFFRACTION2C204 - 446
4X-RAY DIFFRACTION2D682 - 696

+
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