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- PDB-8y7l: Crystal Structure of Nur77 LBD in complex with N-(2'-(4-hydroxypi... -

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Basic information

Entry
Database: PDB / ID: 8y7l
TitleCrystal Structure of Nur77 LBD in complex with N-(2'-(4-hydroxypiperidin-1-yl)-[4,4'-bipyridin]-2-yl)cinnamamide
ComponentsNuclear receptor subfamily 4immunitygroup A member 1
KeywordsTRANSCRIPTION / complex
Function / homology
Function and homology information


neurotransmitter secretion involved in regulation of skeletal muscle contraction / cellular response to corticotropin-releasing hormone stimulus / regulation of type B pancreatic cell proliferation / non-canonical inflammasome complex assembly / detection of lipopolysaccharide / AKT phosphorylates targets in the nucleus / endothelial cell chemotaxis / nuclear glucocorticoid receptor binding / cellular response to fibroblast growth factor stimulus / cell migration involved in sprouting angiogenesis ...neurotransmitter secretion involved in regulation of skeletal muscle contraction / cellular response to corticotropin-releasing hormone stimulus / regulation of type B pancreatic cell proliferation / non-canonical inflammasome complex assembly / detection of lipopolysaccharide / AKT phosphorylates targets in the nucleus / endothelial cell chemotaxis / nuclear glucocorticoid receptor binding / cellular response to fibroblast growth factor stimulus / cell migration involved in sprouting angiogenesis / fat cell differentiation / Constitutive Signaling by AKT1 E17K in Cancer / skeletal muscle cell differentiation / negative regulation of cell cycle / cellular response to vascular endothelial growth factor stimulus / response to electrical stimulus / positive regulation of endothelial cell proliferation / response to amphetamine / lipopolysaccharide binding / Nuclear Receptor transcription pathway / nuclear receptor activity / sequence-specific double-stranded DNA binding / presynapse / DNA-binding transcription activator activity, RNA polymerase II-specific / nuclear membrane / transcription regulator complex / transcription by RNA polymerase II / DNA-binding transcription factor activity, RNA polymerase II-specific / inflammatory response / positive regulation of apoptotic process / protein heterodimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin / regulation of transcription by RNA polymerase II / apoptotic process / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / cytosol
Similarity search - Function
Orphan nuclear receptor, HMR type / Orphan nuclear 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 ...Orphan nuclear receptor, HMR type / Orphan nuclear 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
Similarity search - Domain/homology
: / Nuclear receptor subfamily 4immunitygroup A member 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.683 Å
AuthorsHong, W.B. / Lin, T.W.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Acta Pharm Sin B / Year: 2024
Title: Discovery of a novel exceptionally potent and orally active Nur77 ligand NB1 with a distinct binding mode for cancer therapy
Authors: Chen, J. / Zhao, T. / Hong, W. / Li, H. / Ao, M. / Zhong, Y. / Chen, X. / Qiu, Y. / Wang, X. / Wu, Z. / Lin, T. / Li, B. / Chen, X. / Fang, M.
History
DepositionFeb 4, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 24, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Nuclear receptor subfamily 4immunitygroup A member 1
B: Nuclear receptor subfamily 4immunitygroup A member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,4103
Polymers53,0102
Non-polymers4001
Water68538
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1150 Å2
ΔGint-14 kcal/mol
Surface area22040 Å2
MethodPISA
Unit cell
Length a, b, c (Å)74.781, 76.125, 128.813
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Ens-ID: 1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: PHE / End label comp-ID: PHE / Auth seq-ID: 31 - 267 / Label seq-ID: 2 - 238

Dom-IDComponent-IDAuth asym-IDLabel asym-ID
11AA
22BB

NCS ensembles : (Details: Local NCS retraints between domains: 1 2)

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Components

#1: Protein Nuclear receptor subfamily 4immunitygroup A member 1 / Early response protein NAK1 / Nuclear hormone receptor NUR/77 / Nur77 / Orphan nuclear receptor HMR ...Early response protein NAK1 / Nuclear hormone receptor NUR/77 / Nur77 / Orphan nuclear receptor HMR / Orphan nuclear receptor TR3 / ST-59 / Testicular receptor 3


Mass: 26504.805 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR4A1, GFRP1, HMR, NAK1 / Production host: Escherichia coli (E. coli) / References: UniProt: P22736
#2: Chemical ChemComp-A1D59 / (~{E})-~{N}-[4-[2-(4-oxidanylpiperidin-1-yl)pyridin-4-yl]pyridin-2-yl]-3-phenyl-prop-2-enamide


Mass: 400.473 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H24N4O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 38 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

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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: 3.46 Å3/Da / Density % sol: 64.43 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: PEG4000, Sodium citrate, Glycerol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.9792 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 27, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.68→50 Å / Num. obs: 21249 / % possible obs: 99.9 % / Redundancy: 6.4 % / CC1/2: 0.893 / Net I/σ(I): 4.556
Reflection shellResolution: 2.68→2.73 Å / Num. unique obs: 21249 / CC1/2: 0.898

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Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.683→33.944 Å / Cor.coef. Fo:Fc: 0.925 / Cor.coef. Fo:Fc free: 0.902 / WRfactor Rfree: 0.223 / WRfactor Rwork: 0.188 / SU B: 9.945 / SU ML: 0.203 / Average fsc free: 0.9152 / Average fsc work: 0.9318 / Cross valid method: FREE R-VALUE / ESU R: 0.47 / ESU R Free: 0.285
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2425 1069 5.045 %
Rwork0.2042 20120 -
all0.206 --
obs-21189 99.802 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 39.167 Å2
Baniso -1Baniso -2Baniso -3
1--0.108 Å20 Å20 Å2
2--0.396 Å2-0 Å2
3----0.288 Å2
Refinement stepCycle: LAST / Resolution: 2.683→33.944 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3621 0 30 38 3689
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0133767
X-RAY DIFFRACTIONr_bond_other_d0.0010.0153704
X-RAY DIFFRACTIONr_angle_refined_deg1.5731.6425106
X-RAY DIFFRACTIONr_angle_other_deg1.2581.5838541
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2565467
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.92821.17188
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.93815663
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.5221529
X-RAY DIFFRACTIONr_chiral_restr0.0740.2475
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.024157
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02847
X-RAY DIFFRACTIONr_nbd_refined0.2270.2812
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1840.23212
X-RAY DIFFRACTIONr_nbtor_refined0.1680.21837
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0850.21888
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1490.254
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0570.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1820.219
X-RAY DIFFRACTIONr_nbd_other0.2280.259
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1530.25
X-RAY DIFFRACTIONr_mcbond_it3.4493.9631850
X-RAY DIFFRACTIONr_mcbond_other3.4423.9621849
X-RAY DIFFRACTIONr_mcangle_it5.515.9262308
X-RAY DIFFRACTIONr_mcangle_other5.5095.9272309
X-RAY DIFFRACTIONr_scbond_it3.8374.3331917
X-RAY DIFFRACTIONr_scbond_other3.8364.3361918
X-RAY DIFFRACTIONr_scangle_it6.0896.3622793
X-RAY DIFFRACTIONr_scangle_other6.0886.3662794
X-RAY DIFFRACTIONr_lrange_it11.38273.17715332
X-RAY DIFFRACTIONr_lrange_other11.37873.19415324
X-RAY DIFFRACTIONr_ncsr_local_group_10.130.056919
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)Weight position
11AX-RAY DIFFRACTIONLocal ncs0.130030.05006
12BX-RAY DIFFRACTIONLocal ncs0.130030.05006
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.683-2.7530.348700.271459X-RAY DIFFRACTION98.8365
2.753-2.8280.32760.2481423X-RAY DIFFRACTION99.7339
2.828-2.910.259760.2381369X-RAY DIFFRACTION100
2.91-2.9990.329840.231351X-RAY DIFFRACTION100
2.999-3.0970.316760.2371297X-RAY DIFFRACTION100
3.097-3.2060.274940.2181237X-RAY DIFFRACTION100
3.206-3.3260.211750.1981230X-RAY DIFFRACTION100
3.326-3.4620.244520.2051191X-RAY DIFFRACTION100
3.462-3.6150.244530.2051128X-RAY DIFFRACTION100
3.615-3.7910.227590.2071101X-RAY DIFFRACTION100
3.791-3.9960.243500.1991036X-RAY DIFFRACTION100
3.996-4.2370.185580.185988X-RAY DIFFRACTION100
4.237-4.5280.199560.164922X-RAY DIFFRACTION100
4.528-4.8890.189390.162870X-RAY DIFFRACTION100
4.889-5.3530.185330.175827X-RAY DIFFRACTION100
5.353-5.9790.259380.192731X-RAY DIFFRACTION100
5.979-6.8950.337330.224657X-RAY DIFFRACTION100
6.895-8.4210.169220.169579X-RAY DIFFRACTION100
8.421-11.8120.177140.157459X-RAY DIFFRACTION99.789
11.812-33.9440.337110.319265X-RAY DIFFRACTION93.5593

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