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- PDB-4n5g: Crystal Structure of RXRa LBD complexed with a synthetic modulato... -

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Basic information

Entry
Database: PDB / ID: 4n5g
TitleCrystal Structure of RXRa LBD complexed with a synthetic modulator K8012
ComponentsRetinoic acid receptor RXR-alpha
KeywordsSIGNALING PROTEIN / Retinoid X receptor-alpha nuclear receptor / Nucleus
Function / homology
Function and homology information


positive regulation of transporter activity / retinoic acid-responsive element binding / 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 / positive regulation of thyroid hormone receptor signaling pathway / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / Carnitine shuttle / retinoic acid binding / TGFBR3 expression ...positive regulation of transporter activity / retinoic acid-responsive element binding / 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 / positive regulation of thyroid hormone receptor signaling pathway / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / Carnitine shuttle / retinoic acid binding / TGFBR3 expression / positive regulation of vitamin D receptor signaling pathway / nuclear vitamin D receptor binding / Signaling by Retinoic Acid / DNA binding domain binding / nuclear steroid receptor activity / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / LBD domain binding / Synthesis of bile acids and bile salts / positive regulation of cholesterol efflux / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / retinoic acid receptor signaling pathway / positive regulation of bone mineralization / response to retinoic acid / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / Recycling of bile acids and salts / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / RORA activates gene expression / peroxisome proliferator activated receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / BMAL1:CLOCK,NPAS2 activates circadian gene expression / Activation of gene expression by SREBF (SREBP) / transcription coregulator binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / peptide binding / SUMOylation of intracellular receptors / Heme signaling / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / RNA polymerase II transcription regulator complex / nuclear receptor activity / sequence-specific double-stranded DNA binding / Circadian Clock / double-stranded DNA binding / sequence-specific DNA binding / transcription regulator complex / cell differentiation / receptor complex / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / enzyme binding / positive regulation of transcription by RNA polymerase II / mitochondrion / zinc ion binding / nucleoplasm / identical protein binding / nucleus / cytosol
Similarity search - Function
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 / Zinc finger, C4 type (two domains) ...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 / 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-K09 / Retinoic acid receptor RXR-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.11 Å
AuthorsAleshin, A.E. / Su, Y. / Zhang, X. / Liddington, R.C.
CitationJournal: Chem.Biol. / Year: 2014
Title: Sulindac-Derived RXR alpha Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site.
Authors: Chen, L. / Wang, Z.G. / Aleshin, A.E. / Chen, F. / Chen, J. / Jiang, F. / Alitongbieke, G. / Zeng, Z. / Ma, Y. / Huang, M. / Zhou, H. / Cadwell, G. / Zheng, J.F. / Huang, P.Q. / Liddington, ...Authors: Chen, L. / Wang, Z.G. / Aleshin, A.E. / Chen, F. / Chen, J. / Jiang, F. / Alitongbieke, G. / Zeng, Z. / Ma, Y. / Huang, M. / Zhou, H. / Cadwell, G. / Zheng, J.F. / Huang, P.Q. / Liddington, R.C. / Zhang, X.K. / Su, Y.
History
DepositionOct 9, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 14, 2014Provider: repository / Type: Initial release
Revision 1.1Jun 11, 2014Group: Database references
Revision 1.2Sep 20, 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 / 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 1.3Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

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


Theoretical massNumber of molelcules
Total (without water)109,8276
Polymers109,0784
Non-polymers7492
Water4,972276
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area9840 Å2
ΔGint-61 kcal/mol
Surface area34530 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.585, 98.830, 110.579
Angle α, β, γ (deg.)90.00, 99.02, 90.00
Int Tables number4
Space group name H-MP1211

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Components

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


Mass: 27269.514 Da / Num. of mol.: 4 / Fragment: ligand binding domain (UNP residues 223-462)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RXRA, NR2B1 / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / References: UniProt: P19793
#2: Chemical ChemComp-K09 / 5-(2-{(1Z)-5-fluoro-2-methyl-1-[4-(propan-2-yl)benzylidene]-1H-inden-3-yl}ethyl)-1H-tetrazole


Mass: 374.454 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H23FN4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 276 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46.63 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 20% PEG3330, 0.2M Na Acetate, 100 mM NaCl, 20 mM Tris-Cl, 0.5 mM ligand K-8012, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 293K

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Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 1 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: May 13, 2013 / Details: mirrors
RadiationMonochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.11→37.242 Å / Num. all: 56915 / Num. obs: 48947 / % possible obs: 86 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.6 % / Biso Wilson estimate: 40.3 Å2 / Rmerge(I) obs: 0.079 / Net I/σ(I): 8.1
Reflection shellResolution: 2.11→2.17 Å / Redundancy: 3.4 % / Rmerge(I) obs: 0.8 / Mean I/σ(I) obs: 1.6 / % possible all: 50

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Processing

Software
NameVersionClassification
Blu-Icedata collection
PHASERphasing
PHENIX(phenix.refine: 1.8.2_1309)refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdb entry 1G1U
Resolution: 2.11→37 Å / SU ML: 0.29 / σ(F): 0 / Phase error: 25.81 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2468 2144 4.94 %random
Rwork0.1989 ---
obs0.2012 43378 87.77 %-
all-49423 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.11→37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6390 0 56 276 6722
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0036662
X-RAY DIFFRACTIONf_angle_d0.7289023
X-RAY DIFFRACTIONf_dihedral_angle_d12.3092507
X-RAY DIFFRACTIONf_chiral_restr0.0281023
X-RAY DIFFRACTIONf_plane_restr0.0031150
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.11-2.2250.27981630.25592703X-RAY DIFFRACTION86
2.225-2.25120.33111440.25742860X-RAY DIFFRACTION93
2.2512-2.27860.27551310.25742846X-RAY DIFFRACTION91
2.2786-2.30750.34661430.24092801X-RAY DIFFRACTION88
2.3075-2.33780.3011500.24652855X-RAY DIFFRACTION91
2.3378-2.36980.30231460.23212844X-RAY DIFFRACTION92
2.3698-2.40370.26621540.23672768X-RAY DIFFRACTION89
2.4037-2.43960.34111440.24322766X-RAY DIFFRACTION88
2.4396-2.47770.34611430.25072774X-RAY DIFFRACTION88
2.4777-2.51830.31851310.23662785X-RAY DIFFRACTION88
2.5183-2.56170.30221290.24072429X-RAY DIFFRACTION78
2.5617-2.60830.26091290.22832803X-RAY DIFFRACTION89
2.6083-2.65840.2921720.21812872X-RAY DIFFRACTION94
2.6584-2.71270.32221360.21472820X-RAY DIFFRACTION89
2.7127-2.77160.24861320.20872889X-RAY DIFFRACTION91
2.7716-2.83610.24981590.20492848X-RAY DIFFRACTION91
2.8361-2.9070.27531380.21152795X-RAY DIFFRACTION87
2.907-2.98560.27451590.21442711X-RAY DIFFRACTION89
2.9856-3.07340.31291440.21092677X-RAY DIFFRACTION85
3.0734-3.17250.27641400.22932507X-RAY DIFFRACTION81
3.1725-3.28580.28311520.21392900X-RAY DIFFRACTION92
3.2858-3.41730.24221580.20162826X-RAY DIFFRACTION90
3.4173-3.57270.27431520.19192731X-RAY DIFFRACTION88
3.5727-3.76090.22331530.17812720X-RAY DIFFRACTION88
3.7609-3.99630.23421150.17032649X-RAY DIFFRACTION84
3.9963-4.30440.19641360.16192488X-RAY DIFFRACTION80
4.3044-4.73680.18131450.16622780X-RAY DIFFRACTION88
4.7368-5.42050.22981350.18152659X-RAY DIFFRACTION86
5.4205-6.82240.25921180.21692573X-RAY DIFFRACTION81
6.8224-37.24690.16571370.17642790X-RAY DIFFRACTION89
Refinement TLS params.

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

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
18.79310.50174.24973.93951.45056.5078-0.67980.90840.8421-0.50110.25730.1847-0.94090.13160.40.4168-0.0658-0.01860.33280.09880.35514.992619.050828.0474
23.00790.6029-0.07652.77780.27212.8714-0.06170.16980.22470.0925-0.01970.217-0.0975-0.21680.09950.17810.0365-0.0310.17790.00370.21838.908310.832839.8699
31.36480.84041.87281.22220.73765.0268-0.05470.12270.2026-0.2626-0.07790.075-0.1951-0.3790.06950.23410.06480.0340.2653-0.02160.2634.04886.973132.539
44.1755-1.6117-0.99285.07931.65425.19280.1003-0.191-0.07520.11050.0058-0.26090.340.3703-0.14270.5031-0.0274-0.04210.22970.10510.286915.0115-18.553851.6964
53.7377-0.9367-1.42782.58161.55114.4633-0.03260.5588-0.2479-0.15460.0075-0.55340.68210.71430.04410.41570.1570.06390.475-0.01140.378927.8573-10.476139.1991
63.74840.76710.63863.3621-0.09733.43390.122-0.1365-0.07920.3962-0.0209-0.15950.30850.2728-0.10250.26370.0758-0.02980.16280.00470.211717.9166-1.966250.9689
72.6392-0.0579-0.71743.67515.76689.2003-0.05510.4402-0.23440.61340.1335-0.34470.25630.52450.02690.98280.432-0.23120.7108-0.27050.8623.8714-29.367627.9818
81.3469-0.5281-1.04683.04611.04572.6348-0.15270.8411-0.0611-1.5124-0.07620.3832-1.10410.28840.26971.1897-0.13690.00080.91770.1990.76565.30332.9226-3.0615
91.4341.53920.39553.88191.13322.7889-0.41480.38010.176-0.77630.22770.1385-0.3936-0.10320.19710.4079-0.0298-0.05430.40530.110.3309-1.61933.23744.1217
103.9224-0.6682-0.21313.0533-0.29553.7344-0.02070.340.3829-0.420.1036-0.3989-0.06340.7132-0.05360.3652-0.05540.05210.4625-0.02690.272910.6255-8.48733.7079
115.55190.4218-0.17932.20854.28638.59050.21570.28780.1704-0.5778-0.5354-0.0424-0.6412-0.12050.23580.594-0.0286-0.02820.4310.12580.418718.672716.062119.0677
123.23440.1279-1.87023.19591.58377.1110.07480.2079-0.5441-0.05560.0326-0.26931.26310.3491-0.0440.69110.2067-0.16440.4898-0.14020.480516.689-33.243721.903
133.59022.3464-2.50483.51610.46613.7499-0.5185-0.6879-0.33680.03920.2560.05230.65090.00480.22290.65140.1791-0.08010.4331-0.03850.32771.1079-27.899422.9062
140.93610.15481.02350.7488-0.02742.31950.09620.1663-0.2986-0.12060.0598-0.02180.25380.1464-0.15260.38860.0288-0.01580.2787-0.06630.30235.0709-23.892917.157
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(CHAIN A AND RESID 263:301)
2X-RAY DIFFRACTION2(CHAIN A AND RESID 302:405)
3X-RAY DIFFRACTION3(CHAIN A AND RESID 406:458)
4X-RAY DIFFRACTION4(CHAIN B AND RESID 231:302)
5X-RAY DIFFRACTION5(CHAIN B AND RESID 303:359)
6X-RAY DIFFRACTION6(CHAIN B AND RESID 360:437)
7X-RAY DIFFRACTION7(CHAIN B AND RESID 438:458)
8X-RAY DIFFRACTION8(CHAIN C AND RESID 231:264)
9X-RAY DIFFRACTION9(CHAIN C AND RESID 265:301)
10X-RAY DIFFRACTION10(CHAIN C AND RESID 302:437)
11X-RAY DIFFRACTION11(CHAIN C AND RESID 438:458)
12X-RAY DIFFRACTION12(CHAIN D AND RESID 263:301)
13X-RAY DIFFRACTION13(CHAIN D AND RESID 302:333)
14X-RAY DIFFRACTION14(CHAIN D AND RESID 334:458)

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