[English] 日本語
Yorodumi
- PDB-7wmj: A novel chemical derivative(71) of THRB agonist -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7wmj
TitleA novel chemical derivative(71) of THRB agonist
Components
  • Isoform Beta-2 of Thyroid hormone receptor beta
  • Nuclear receptor coactivator 2
KeywordsTRANSCRIPTION / Transcription factor / ligand
Function / homology
Function and homology information


retinal cone cell apoptotic process / negative regulation of female receptivity / female courtship behavior / thyroid hormone binding / retinal cone cell development / thyroid hormone receptor signaling pathway / positive regulation of thyroid hormone receptor signaling pathway / cellular response to thyroid hormone stimulus / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / regulation of heart contraction ...retinal cone cell apoptotic process / negative regulation of female receptivity / female courtship behavior / thyroid hormone binding / retinal cone cell development / thyroid hormone receptor signaling pathway / positive regulation of thyroid hormone receptor signaling pathway / cellular response to thyroid hormone stimulus / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / regulation of heart contraction / type I pneumocyte differentiation / locomotor rhythm / aryl hydrocarbon receptor binding / cellular response to Thyroglobulin triiodothyronine / regulation of lipid metabolic process / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / cellular response to hormone stimulus / Recycling of bile acids and salts / transcription regulator inhibitor activity / retinoic acid receptor signaling pathway / : / positive regulation of adipose tissue development / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / regulation of cellular response to insulin stimulus / BMAL1:CLOCK,NPAS2 activates circadian expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / response to progesterone / nuclear receptor binding / negative regulation of smoothened signaling pathway / SUMOylation of intracellular receptors / circadian regulation of gene expression / mRNA transcription by RNA polymerase II / Heme signaling / sensory perception of sound / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Cytoprotection by HMOX1 / chromatin DNA binding / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / RNA polymerase II transcription regulator complex / transcription coactivator binding / nuclear receptor activity / sequence-specific double-stranded DNA binding / : / HATs acetylate histones / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / transcription regulator complex / Estrogen-dependent gene expression / DNA-binding transcription factor activity, RNA polymerase II-specific / cell differentiation / transcription coactivator activity / protein dimerization activity / nuclear body / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein domain specific binding / DNA-templated transcription / chromatin binding / regulation of DNA-templated transcription / chromatin / enzyme binding / 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 / cytoplasm
Similarity search - Function
Thyroid hormone 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 ...Thyroid hormone 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 / Nuclear receptor coactivators bHLH domain / 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 / PAS domain superfamily / 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
Similarity search - Domain/homology
Chem-9IL / Thyroid hormone receptor beta / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.81 Å
AuthorsYao, B.Q. / Li, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31770814 China
Citation
Journal: J.Med.Chem. / Year: 2022
Title: Discovery of a Highly Selective and H435R-Sensitive Thyroid Hormone Receptor beta Agonist.
Authors: Li, Q. / Yao, B. / Zhao, S. / Lu, Z. / Zhang, Y. / Xiang, Q. / Wu, X. / Yu, H. / Zhang, C. / Li, J. / Zhuang, X. / Wu, D. / Li, Y. / Xu, Y.
#1: Journal: iScience / Year: 2019
Title: Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance.
Authors: Yao, B. / Wei, Y. / Zhang, S. / Tian, S. / Xu, S. / Wang, R. / Zheng, W. / Li, Y.
History
DepositionJan 14, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 18, 2022Provider: repository / Type: Initial release
Revision 1.1Jun 8, 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 1.2Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform Beta-2 of Thyroid hormone receptor beta
B: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,2613
Polymers30,7612
Non-polymers5001
Water81145
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1000 Å2
ΔGint-8 kcal/mol
Surface area11540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)105.742, 105.742, 56.764
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein Isoform Beta-2 of Thyroid hormone receptor beta


Mass: 29410.996 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: THRB / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P10828
#2: Protein/peptide Nuclear receptor coactivator 2


Mass: 1349.576 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SRC2 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q15596
#3: Chemical ChemComp-9IL / 2-[[7-[2,6-dimethyl-4-(phenylcarbonyl)phenoxy]-1-methoxy-4-oxidanyl-isoquinolin-3-yl]carbonylamino]ethanoic acid


Mass: 500.499 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H24N2O7 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 45 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.58 Å3/Da / Density % sol: 52.31 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 25% v/v ethylene glycol.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: May 9, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.81→50 Å / Num. obs: 8285 / % possible obs: 99.9 % / Redundancy: 12 % / Rmerge(I) obs: 0.129 / Rpim(I) all: 0.039 / Rrim(I) all: 0.135 / Χ2: 0.964 / Net I/σ(I): 5 / Num. measured all: 99739
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.81-2.869.91.3474170.6850.4331.4170.821100
2.86-2.9111.71.183820.8240.3521.2320.832100
2.91-2.9712.71.0644020.8410.3061.1070.836100
2.97-3.0312.40.914160.8690.2630.9480.867100
3.03-3.09130.8163930.8980.2330.8490.87100
3.09-3.1612.70.6344130.9330.1840.660.885100
3.16-3.2412.50.4874010.9590.1410.5070.874100
3.24-3.3312.20.4024080.9830.1190.4190.96100
3.33-3.4311.60.3134010.9750.0950.3270.995100
3.43-3.54120.2434140.9830.0730.2541.044100
3.54-3.6712.60.2713970.9740.0790.2831.384100
3.67-3.8112.60.1994140.9860.0580.2071.337100
3.81-3.9912.80.1584150.9950.0450.1651.153100
3.99-4.212.40.1264070.9930.0370.1311.094100
4.2-4.4611.70.1174220.9940.0360.1221.095100
4.46-4.811.90.1014150.9960.030.1051.003100
4.8-5.2912.70.14240.9940.0290.1040.935100
5.29-6.0512.30.0934240.9970.0270.0970.809100
6.05-7.6211.10.0754410.9950.0230.0790.718100
7.62-5010.30.0674790.9850.0230.0710.71499

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
HKL-2000data scaling
PDB_EXTRACT3.27data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6KKB

6kkb


Resolution: 2.81→38.72 Å / Cor.coef. Fo:Fc: 0.907 / Cor.coef. Fo:Fc free: 0.866 / SU B: 32.276 / SU ML: 0.315 / SU R Cruickshank DPI: 0.3384 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.411 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2738 388 4.9 %RANDOM
Rwork0.2268 ---
obs0.2292 7494 95.41 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 118.88 Å2 / Biso mean: 44.603 Å2 / Biso min: 15.02 Å2
Baniso -1Baniso -2Baniso -3
1--0.43 Å20 Å20 Å2
2---0.43 Å20 Å2
3---0.87 Å2
Refinement stepCycle: final / Resolution: 2.81→38.72 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1921 0 37 45 2003
Biso mean--50.99 34.57 -
Num. residues----240
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0132002
X-RAY DIFFRACTIONr_bond_other_d0.0010.0171919
X-RAY DIFFRACTIONr_angle_refined_deg1.2161.6412706
X-RAY DIFFRACTIONr_angle_other_deg1.2511.5774425
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6645235
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.2222.14398
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.5515354
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.881511
X-RAY DIFFRACTIONr_chiral_restr0.0620.2255
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022180
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02439
LS refinement shellResolution: 2.811→2.884 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.402 15 -
Rwork0.293 285 -
all-300 -
obs--49.92 %
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)
11.48010.5093-0.47971.9364-0.44741.1365-0.15420.0729-0.07770.12510.0228-0.1532-0.1786-0.06370.13150.1551-0.0622-0.0350.1169-0.02430.034434.4562-17.20816.4737
210.8039-0.1194-0.29727.872.10684.45980.2490.4749-0.2053-0.0810.00660.436-0.1973-0.1459-0.25560.15310.0518-0.02860.0513-0.01320.078426.4821-0.099-0.2763
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A211 - 459
2X-RAY DIFFRACTION2B741 - 751

+
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