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- PDB-5drj: Crystal Structure of the ER-alpha Ligand-binding Domain in comple... -

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Basic information

Entry
Database: PDB / ID: 5drj
TitleCrystal Structure of the ER-alpha Ligand-binding Domain in complex with a dichloro-substituted, 3-methyl 2,5-diarylthiophene-core ligand 4,4'-(3-methylthiene-2,5-diyl)bis(3-chlorophenol)
Components
  • Estrogen receptor
  • Nuclear receptor coactivator 2
KeywordsTRANSCRIPTION / Nuclear receptor / transcription factor / ligand binding / protein-ligand complex
Function / homology
Function and homology information


regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / epithelial cell development / vagina development / locomotor rhythm / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / aryl hydrocarbon receptor binding / TFIIB-class transcription factor binding / androgen metabolic process / regulation of lipid metabolic process / steroid hormone receptor signaling pathway / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / mammary gland alveolus development / cellular response to estrogen stimulus / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / estrogen response element binding / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear receptor-mediated steroid hormone signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / Recycling of bile acids and salts / cellular response to hormone stimulus / 14-3-3 protein binding / protein localization to chromatin / estrogen receptor signaling pathway / positive regulation of adipose tissue development / RORA activates gene expression / peroxisome proliferator activated receptor signaling pathway / steroid binding / nitric-oxide synthase regulator activity / Regulation of lipid metabolism by PPARalpha / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / TBP-class protein binding / regulation of cellular response to insulin stimulus / ESR-mediated signaling / BMAL1:CLOCK,NPAS2 activates circadian gene expression / transcription corepressor binding / negative regulation of miRNA transcription / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / positive regulation of nitric-oxide synthase activity / cellular response to estradiol stimulus / transcription coregulator binding / response to progesterone / nuclear receptor binding / stem cell differentiation / nuclear estrogen receptor binding / positive regulation of DNA-binding transcription factor activity / 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 / euchromatin / negative regulation of DNA-binding transcription factor activity / PPARA activates gene expression / Cytoprotection by HMOX1 / beta-catenin binding / transcription coactivator binding / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / response to estrogen / RNA polymerase II transcription regulator complex / Constitutive Signaling by Aberrant PI3K in Cancer / male gonad development / nuclear receptor activity / Regulation of RUNX2 expression and activity / positive regulation of fibroblast proliferation / sequence-specific double-stranded DNA binding / positive regulation of nitric oxide biosynthetic process / Ovarian tumor domain proteases / Circadian Clock / PIP3 activates AKT signaling / response to estradiol / HATs acetylate histones / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / regulation of inflammatory response / positive regulation of cytosolic calcium ion concentration / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / fibroblast proliferation / DNA-binding transcription activator activity, RNA polymerase II-specific
Similarity search - Function
Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / Nuclear receptor coactivator, DUF1518 ...Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / 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
4,4'-(3-methylthiene-2,5-diyl)bis(3-chlorophenol) / Estrogen receptor / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.07 Å
AuthorsNwachukwu, J.C. / Srinivasan, S. / Zheng, Y. / Wang, S. / Min, J. / Dong, C. / Liao, Z. / Cavett, V. / Nowak, J. / Houtman, R. ...Nwachukwu, J.C. / Srinivasan, S. / Zheng, Y. / Wang, S. / Min, J. / Dong, C. / Liao, Z. / Cavett, V. / Nowak, J. / Houtman, R. / Carlson, K.E. / Josan, J.S. / Elemento, O. / Katzenellenbogen, J.A. / Zhou, H.B. / Nettles, K.W.
CitationJournal: Mol.Syst.Biol. / Year: 2016
Title: Predictive features of ligand-specific signaling through the estrogen receptor.
Authors: Nwachukwu, J.C. / Srinivasan, S. / Zheng, Y. / Wang, S. / Min, J. / Dong, C. / Liao, Z. / Nowak, J. / Wright, N.J. / Houtman, R. / Carlson, K.E. / Josan, J.S. / Elemento, O. / ...Authors: Nwachukwu, J.C. / Srinivasan, S. / Zheng, Y. / Wang, S. / Min, J. / Dong, C. / Liao, Z. / Nowak, J. / Wright, N.J. / Houtman, R. / Carlson, K.E. / Josan, J.S. / Elemento, O. / Katzenellenbogen, J.A. / Zhou, H.B. / Nettles, K.W.
History
DepositionSep 15, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 4, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Estrogen receptor
B: Estrogen receptor
C: Nuclear receptor coactivator 2
D: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,6356
Polymers61,9334
Non-polymers7022
Water3,819212
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5260 Å2
ΔGint-25 kcal/mol
Surface area20140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)55.950, 82.510, 58.510
Angle α, β, γ (deg.)90.000, 110.610, 90.000
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein Estrogen receptor / ER / ER-alpha / Estradiol receptor / Nuclear receptor subfamily 3 group A member 1


Mass: 29299.535 Da / Num. of mol.: 2 / Mutation: Y537S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P03372
#2: Protein/peptide Nuclear receptor coactivator 2


Mass: 1666.943 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: This sequence occurs naturally in humans / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596*PLUS
#3: Chemical ChemComp-5EU / 4,4'-(3-methylthiene-2,5-diyl)bis(3-chlorophenol)


Mass: 351.247 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C17H12Cl2O2S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 212 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 2.07 Å3/Da / Density % sol: 40.5 %
Crystal growTemperature: 294 K / Method: vapor diffusion, hanging drop / pH: 8.3 / Details: 15% PEG 3350, 0.05M MgCl2, 0.067M NaCl, 0.1M Tris

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 27, 2012
RadiationMonochromator: Side scattering bent cube i-beam single crystal asymmetric cut 4.965 degs
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.07→50 Å / Num. obs: 30246 / % possible obs: 98 % / Redundancy: 6.8 % / Rmerge(I) obs: 0.073 / Χ2: 0.768 / Net I/av σ(I): 26.128 / Net I/σ(I): 6.1 / Num. measured all: 204410
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
2.07-2.116.20.815150.4697.9
2.11-2.146.30.69414900.47898.3
2.14-2.195.90.60714740.47295.3
2.19-2.236.40.514580.47496.2
2.23-2.2870.38615270.50798.8
2.28-2.3370.36415170.49498.3
2.33-2.3970.3115030.51898.7
2.39-2.4570.25115340.51998
2.45-2.5370.21814970.56999.2
2.53-2.616.80.18115320.56299.4
2.61-2.76.90.15715330.58698.7
2.7-2.816.30.1314760.6596.1
2.81-2.946.90.10714990.71497.1
2.94-3.097.20.08515350.79999.6
3.09-3.297.10.07615540.90199.7
3.29-3.546.90.06315101.0699.1
3.54-3.96.80.05615261.18198.2
3.9-4.466.50.05314641.43794.6
4.46-5.627.10.05415571.3799
5.62-506.80.05115451.47397

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Processing

Software
NameVersionClassification
PHENIX1.9_1690refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QA8

2qa8


Resolution: 2.07→47.006 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 25.1 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2223 1695 6.64 %
Rwork0.1848 23843 -
obs0.1873 25538 82.5 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 143.63 Å2 / Biso mean: 42.5359 Å2 / Biso min: 8.24 Å2
Refinement stepCycle: final / Resolution: 2.07→47.006 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3875 0 44 212 4131
Biso mean--40.96 42.04 -
Num. residues----496
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0034036
X-RAY DIFFRACTIONf_angle_d0.6785475
X-RAY DIFFRACTIONf_chiral_restr0.024645
X-RAY DIFFRACTIONf_plane_restr0.003683
X-RAY DIFFRACTIONf_dihedral_angle_d12.9331480
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 12

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.0578-2.11840.2937240.247140843217
2.1184-2.18670.3095780.21321137121548
2.1867-2.26490.34311280.22431716184472
2.2649-2.35560.28191510.20782110226188
2.3556-2.46280.22971520.20392184233692
2.4628-2.59260.25531630.20372263242695
2.5926-2.7550.24271500.20692298244895
2.755-2.96770.23591770.21142249242694
2.9677-3.26630.23621680.2012389255799
3.2663-3.73880.22651730.17652371254499
3.7388-4.70980.16741500.15222319246996
4.7098-47.01830.19861810.16872399258098
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)
15.01560.8685-0.45055.3826-1.24515.55670.6536-0.64781.18420.9199-0.54810.0185-0.75820.9248-0.11280.6212-0.2586-0.00360.4361-0.13330.3722-1.095-4.82465.1882
24.92531.8066-1.18996.8412-1.28016.63310.2559-0.4743-0.49660.2136-0.55080.92390.7692-0.45480.26670.33180.03820.05430.34960.00760.4329-21.1344-29.85027.1776
35.80680.5685-1.38293.8452-1.97634.6250.0799-0.0076-0.0531-0.08120.06790.4206-0.1598-0.6099-0.17790.2150.00210.02450.24920.01580.1581-21.24-20.87641.1614
43.7098-0.6056-0.32334.3095-1.24034.15260.18120.17390.4369-0.0035-0.07320.0107-0.3264-0.2625-0.08540.23570.00290.0830.1920.0230.1963-13.7262-12.2841-4.4039
54.4505-0.0872-1.09924.9575-2.37715.2523-0.198-0.5321-0.80460.0621-0.1521-0.08570.80580.23280.25150.36050.03310.08090.19970.06630.3429-11.5105-33.11813.1841
64.1014-0.1836-4.5256.152-4.13048.1204-0.35861.2082-0.9128-0.75130.23311.12581.5125-1.51830.23321.0363-0.20660.1410.4409-0.10370.6928-18.8896-38.8546-7.0089
77.71464.3553.9015.81992.26234.76820.08350.0833-0.9417-0.0787-0.093-0.09990.9369-0.00530.05590.40430.02650.04710.2405-0.00580.2988-7.2194-31.5778-6.8656
88.6273-1.4243-0.21755.70480.52693.66260.12090.26050.37970.1205-0.1744-0.1762-0.42750.25760.19510.2859-0.08830.0460.1829-0.01290.1546-4.8855-13.8296-5.2521
93.7608-1.2320.85092.10610.11453.94320.113-0.3570.67980.3369-0.1795-0.5565-0.73440.47150.28940.4707-0.2014-0.07510.4014-0.00590.30663.9003-8.5599-3.3653
103.65080.472-0.36422.7308-0.29233.6191-0.0144-0.108-0.33980.0545-0.06270.01780.0527-0.02950.0920.3079-0.00790.01750.17980.00430.151-6.2977-21.8288-11.3434
119.78171.0956-0.25254.93190.38965.1792-0.2560.6315-0.5755-0.25860.0181.19170.9187-0.88990.00250.3347-0.13330.01320.52430.02260.591-29.1616-20.4075-9.4004
122.40110.6505-1.03993.1005-0.7385.2475-0.11020.2539-0.0221-0.1821-0.0078-0.0370.2793-0.04050.0620.1779-0.00630.0210.21220.00510.1755-1.2886-19.6179-33.4319
135.7277-1.68160.23246.1271-0.50225.6469-0.0350.111-0.05520.4210.1090.4763-0.3466-0.2817-0.07150.23740.02570.06530.26610.03640.1489-4.3194-14.7972-24.2124
144.21530.86020.80923.7590.59465.5785-0.06240.1444-0.20080.0104-0.03990.13860.2137-0.02050.08680.2029-0.00350.04310.17010.03160.1512-2.3247-20.1724-21.6481
155.26671.7255-1.86526.4390.17331.68950.70140.41790.8822-0.0664-0.84010.4225-0.6533-0.6877-0.06230.44280.10440.13890.41570.04880.5504-26.1662-5.8863-1.5962
169.7715-1.14195.49694.87510.34034.77830.13041.4147-1.5894-0.1272-0.11790.03521.5570.5655-0.18180.80990.04230.11780.358-0.11890.4593-1.2451-37.4266-35.1175
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 305 through 321 )A0
2X-RAY DIFFRACTION2chain 'A' and (resid 322 through 338 )A0
3X-RAY DIFFRACTION3chain 'A' and (resid 339 through 363 )A0
4X-RAY DIFFRACTION4chain 'A' and (resid 364 through 394 )A0
5X-RAY DIFFRACTION5chain 'A' and (resid 395 through 411 )A0
6X-RAY DIFFRACTION6chain 'A' and (resid 412 through 420 )A0
7X-RAY DIFFRACTION7chain 'A' and (resid 421 through 437 )A0
8X-RAY DIFFRACTION8chain 'A' and (resid 438 through 472 )A0
9X-RAY DIFFRACTION9chain 'A' and (resid 473 through 496 )A0
10X-RAY DIFFRACTION10chain 'A' and (resid 497 through 529 )A0
11X-RAY DIFFRACTION11chain 'A' and (resid 530 through 548 )A0
12X-RAY DIFFRACTION12chain 'B' and (resid 305 through 410 )B0
13X-RAY DIFFRACTION13chain 'B' and (resid 411 through 469 )B0
14X-RAY DIFFRACTION14chain 'B' and (resid 470 through 549 )B0
15X-RAY DIFFRACTION15chain 'C' and (resid 687 through 696 )C0
16X-RAY DIFFRACTION16chain 'D' and (resid 687 through 696 )D0

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