[English] 日本語
Yorodumi
- PDB-3l0e: X-ray crystal structure of a Potent Liver X Receptor Modulator -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3l0e
TitleX-ray crystal structure of a Potent Liver X Receptor Modulator
Components
  • Nuclear receptor coactivator 2
  • Oxysterols receptor LXR-beta
KeywordsTRANSCRIPTION / hLXR-beta / human Liver X Receptor-beta / sulfonamide modulator / DNA-binding / Metal-binding / Nucleus / Receptor / Transcription regulation / Zinc-finger / Activator / Phosphoprotein
Function / homology
Function and homology information


positive regulation of secretion of lysosomal enzymes / positive regulation of high-density lipoprotein particle assembly / positive regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / positive regulation of cholesterol transport / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / positive regulation of lipoprotein lipase activity / apolipoprotein A-I receptor binding / positive regulation of triglyceride biosynthetic process ...positive regulation of secretion of lysosomal enzymes / positive regulation of high-density lipoprotein particle assembly / positive regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / positive regulation of cholesterol transport / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / positive regulation of lipoprotein lipase activity / apolipoprotein A-I receptor binding / positive regulation of triglyceride biosynthetic process / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / positive regulation of lipid storage / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / positive regulation of fatty acid biosynthetic process / negative regulation of lipid transport / negative regulation of cold-induced thermogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of type II interferon-mediated signaling pathway / negative regulation of cholesterol storage / locomotor rhythm / aryl hydrocarbon receptor binding / positive regulation of cholesterol efflux / negative regulation of macrophage derived foam cell differentiation / regulation of lipid metabolic process / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / 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 / Recycling of bile acids and salts / regulation of cellular response to insulin stimulus / cellular response to hormone stimulus / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / VLDLR internalisation and degradation / positive regulation of protein metabolic process / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / 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 receptor binding / negative regulation of proteolysis / circadian regulation of gene expression / SUMOylation of intracellular receptors / Heme signaling / mRNA transcription by RNA polymerase II / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / chromatin DNA binding / Transcriptional regulation of white adipocyte differentiation / positive regulation of miRNA transcription / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / Circadian Clock / HATs acetylate histones / ATPase binding / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / cell differentiation / transcription coactivator activity / protein dimerization activity / nuclear body / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / negative regulation of DNA-templated transcription / chromatin binding / chromatin / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Liver X receptor / Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / 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 ...Liver X receptor / Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / 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-G58 / Oxysterols receptor LXR-beta / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsGampe Jr., R.T.
CitationJournal: J.Med.Chem. / Year: 2010
Title: Discovery of tertiary sulfonamides as potent liver X receptor antagonists.
Authors: Zuercher, W.J. / Buckholz, R.G. / Campobasso, N. / Collins, J.L. / Galardi, C.M. / Gampe, R.T. / Hyatt, S.M. / Merrihew, S.L. / Moore, J.T. / Oplinger, J.A. / Reid, P.R. / Spearing, P.K. / ...Authors: Zuercher, W.J. / Buckholz, R.G. / Campobasso, N. / Collins, J.L. / Galardi, C.M. / Gampe, R.T. / Hyatt, S.M. / Merrihew, S.L. / Moore, J.T. / Oplinger, J.A. / Reid, P.R. / Spearing, P.K. / Stanley, T.B. / Stewart, E.L. / Willson, T.M.
History
DepositionDec 9, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 7, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Refinement description / Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Revision 1.3Oct 13, 2021Group: Database references / Derived calculations / Category: 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 1.4Sep 6, 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: Oxysterols receptor LXR-beta
B: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,7383
Polymers30,1902
Non-polymers5481
Water1,36976
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1320 Å2
ΔGint-5 kcal/mol
Surface area12440 Å2
MethodPISA
2
A: Oxysterols receptor LXR-beta
B: Nuclear receptor coactivator 2
hetero molecules

A: Oxysterols receptor LXR-beta
B: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)61,4776
Polymers60,3814
Non-polymers1,0962
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_555-y,-x,-z+1/41
Buried area4650 Å2
ΔGint-21 kcal/mol
Surface area22860 Å2
MethodPISA
Unit cell
Length a, b, c (Å)114.855, 114.855, 56.407
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number91
Space group name H-MP4122

-
Components

#1: Protein Oxysterols receptor LXR-beta / Liver X receptor beta / Nuclear orphan receptor LXR-beta / Nuclear receptor subfamily 1 group H ...Liver X receptor beta / Nuclear orphan receptor LXR-beta / Nuclear receptor subfamily 1 group H member 2 / Ubiquitously-expressed nuclear receptor / Nuclear receptor NER


Mass: 28711.670 Da / Num. of mol.: 1 / Fragment: UNP residues 213-461 / Mutation: C238S, C326S, R361S, R362S, Q445A, K447A, K448A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H2, LXRB, NER, UNR / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P55055
#2: Protein/peptide Nuclear receptor coactivator 2 / / NCoA-2 / Transcriptional intermediary factor 2 / hTIF2


Mass: 1478.756 Da / Num. of mol.: 1 / Fragment: UNP residues 740-751 / Source method: obtained synthetically / Details: This sequence occurs naturally in humans / References: UniProt: Q15596
#3: Chemical ChemComp-G58 / N-(2-chloro-6-fluorobenzyl)-1-methyl-N-{[3'-(methylsulfonyl)biphenyl-4-yl]methyl}-1H-imidazole-4-sulfonamide


Mass: 548.049 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H23ClFN3O4S2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 76 / 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: 3.08 Å3/Da / Density % sol: 60.08 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 1:1 (v/v) ratio of the protein complex and PEG 2K MME 20%, 0.2mM MgCl2, 0.1mM TRIS HCl, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Feb 25, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→30 Å / Num. all: 16723 / Num. obs: 16707 / % possible obs: 94 % / Observed criterion σ(I): -3 / Redundancy: 10.8 % / Biso Wilson estimate: 43 Å2 / Rmerge(I) obs: 0.065 / Net I/σ(I): 34
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 10.2 % / Rmerge(I) obs: 0.4 / Mean I/σ(I) obs: 4.3 / Num. unique all: 991 / % possible all: 79.5

-
Processing

Software
NameVersionClassification
PHASERPhenixphasing
REFMAC6.0.2refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1PQ9

1pq9


Resolution: 2.3→27.74 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.955 / SU B: 16.599 / SU ML: 0.178 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.253 / ESU R Free: 0.203 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23661 533 3.2 %RANDOM
Rwork0.2021 ---
obs0.20316 16167 96.92 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 39.452 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 2.3→27.74 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2028 0 36 76 2140
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0222112
X-RAY DIFFRACTIONr_bond_other_d0.0010.021427
X-RAY DIFFRACTIONr_angle_refined_deg1.1941.992869
X-RAY DIFFRACTIONr_angle_other_deg0.90233481
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.0855255
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.46824.7100
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.32315364
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.0071514
X-RAY DIFFRACTIONr_chiral_restr0.0560.2322
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212373
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02431
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_it0.5481.51282
X-RAY DIFFRACTIONr_mcbond_other0.0711.5503
X-RAY DIFFRACTIONr_mcangle_it1.05222070
X-RAY DIFFRACTIONr_scbond_it1.3463830
X-RAY DIFFRACTIONr_scangle_it2.3044.5798
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.3→2.363 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.477 38 -
Rwork0.285 927 -
obs--77.89 %
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)
13.8591-0.85121.25571.9151-1.22452.0284-0.05550.39730.2397-0.17460.0175-0.1979-0.0036-0.05050.0380.1401-0.05190.04890.1397-0.03640.095520.673-40.4391.16
27.7952-8.74270.78920.04395.53324.5367-0.3436-1.0235-0.58371.15490.12781.43360.6666-0.81550.21590.2028-0.1237-0.02220.41390.02250.21867.289-41.84415.215
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A220 - 460
2X-RAY DIFFRACTION2B741 - 750

+
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