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- PDB-4e73: Crystal structure of JNK1beta-JIP in complex with an azaquinolone... -

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Basic information

Entry
Database: PDB / ID: 4.0E+73
TitleCrystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor
Components
  • C-Jun-amino-terminal kinase-interacting protein 1
  • Mitogen-activated protein kinase 8
KeywordsTransferase/Transferase Inhibitor / Kinase / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


positive regulation of cell killing / dentate gyrus mossy fiber / JUN phosphorylation / regulation of CD8-positive, alpha-beta T cell proliferation / regulation of DNA replication origin binding / Interleukin-38 signaling / Activation of BMF and translocation to mitochondria / basal dendrite / Activation of BIM and translocation to mitochondria / JUN kinase activity ...positive regulation of cell killing / dentate gyrus mossy fiber / JUN phosphorylation / regulation of CD8-positive, alpha-beta T cell proliferation / regulation of DNA replication origin binding / Interleukin-38 signaling / Activation of BMF and translocation to mitochondria / basal dendrite / Activation of BIM and translocation to mitochondria / JUN kinase activity / WNT5:FZD7-mediated leishmania damping / negative regulation of JUN kinase activity / MAP-kinase scaffold activity / protein serine/threonine kinase binding / JUN kinase binding / positive regulation of cyclase activity / histone deacetylase regulator activity / positive regulation of NLRP3 inflammasome complex assembly / DSCAM interactions / NRAGE signals death through JNK / protein kinase inhibitor activity / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / kinesin binding / regulation of JNK cascade / regulation of macroautophagy / mitogen-activated protein kinase / negative regulation of intrinsic apoptotic signaling pathway / stress-activated MAPK cascade / response to mechanical stimulus / response to UV / JNK cascade / vesicle-mediated transport / cellular response to cadmium ion / cellular response to amino acid starvation / positive regulation of protein metabolic process / NRIF signals cell death from the nucleus / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / negative regulation of protein binding / mitochondrial membrane / FCERI mediated MAPK activation / positive regulation of JNK cascade / peptidyl-threonine phosphorylation / regulation of circadian rhythm / cellular response to reactive oxygen species / cellular response to mechanical stimulus / histone deacetylase binding / rhythmic process / regulation of protein localization / cellular senescence / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / cellular response to oxidative stress / peptidyl-serine phosphorylation / protein phosphatase binding / Oxidative Stress Induced Senescence / response to oxidative stress / cellular response to lipopolysaccharide / positive regulation of apoptotic process / axon / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / dendrite / synapse / endoplasmic reticulum membrane / positive regulation of gene expression / regulation of DNA-templated transcription / negative regulation of apoptotic process / perinuclear region of cytoplasm / enzyme binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
JIP1, SH3 domain / : / Mitogen-activated protein (MAP) kinase, JNK / Phosphotyrosine interaction domain (PTB/PID) / Phosphotyrosine interaction domain (PID) profile. / Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain / PTB/PI domain / Variant SH3 domain / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. ...JIP1, SH3 domain / : / Mitogen-activated protein (MAP) kinase, JNK / Phosphotyrosine interaction domain (PTB/PID) / Phosphotyrosine interaction domain (PID) profile. / Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain / PTB/PI domain / Variant SH3 domain / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / PH-like domain superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-0NR / Mitogen-activated protein kinase 8 / C-Jun-amino-terminal kinase-interacting protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.27 Å
AuthorsLukacs, C.M. / Janson, C.A.
CitationJournal: ACS Med Chem Lett / Year: 2012
Title: Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor.
Authors: Haynes, N.E. / Scott, N.R. / Chen, L.C. / Janson, C.A. / Li, J.K. / Lukacs, C.M. / Railkar, A. / Tozzo, E. / Whittard, T. / Brown, N.F. / Cheung, A.W.
History
DepositionMar 16, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 29, 2013Provider: repository / Type: Initial release
Revision 1.1Sep 24, 2014Group: Database references
Revision 1.2Sep 13, 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Mitogen-activated protein kinase 8
B: C-Jun-amino-terminal kinase-interacting protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,4683
Polymers43,9062
Non-polymers5631
Water1,60389
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1180 Å2
ΔGint-6 kcal/mol
Surface area15800 Å2
MethodPISA
Unit cell
Length a, b, c (Å)62.901, 79.840, 85.524
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Mitogen-activated protein kinase 8 / MAP kinase 8 / MAPK 8 / JNK-46 / Stress-activated protein kinase 1c / SAPK1c / Stress-activated ...MAP kinase 8 / MAPK 8 / JNK-46 / Stress-activated protein kinase 1c / SAPK1c / Stress-activated protein kinase JNK1 / c-Jun N-terminal kinase 1


Mass: 42588.191 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK8, JNK1, PRKM8, SAPK1, SAPK1C / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: P45983, mitogen-activated protein kinase
#2: Protein/peptide C-Jun-amino-terminal kinase-interacting protein 1 / JIP-1 / JNK-interacting protein 1 / Islet-brain 1 / IB-1 / JNK MAP kinase scaffold protein 1 / ...JIP-1 / JNK-interacting protein 1 / Islet-brain 1 / IB-1 / JNK MAP kinase scaffold protein 1 / Mitogen-activated protein kinase 8-interacting protein 1


Mass: 1317.598 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9UQF2
#3: Chemical ChemComp-0NR / methyl 3-(4-{[(1R,2S,3S,5S,7s)-5-aminotricyclo[3.3.1.1~3,7~]dec-2-yl]carbamoyl}benzyl)-4-oxo-1-phenyl-1,4-dihydro-1,8-naphthyridine-2-carboxylate


Mass: 562.658 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H34N4O4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 89 / Source method: isolated from a natural source / Formula: H2O

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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: 2.45 Å3/Da / Density % sol: 49.71 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6
Details: 13-16% PEG 3350, 0.1M Ada pH 6.0, 10 mM DTT, VAPOR DIFFUSION, SITTING DROP, temperature 298K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.9793 Å
DetectorType: RAYONIX MX225HE / Detector: CCD / Date: Mar 4, 2010
RadiationMonochromator: diamond / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9793 Å / Relative weight: 1
ReflectionResolution: 2.27→27.7 Å / Num. all: 20301 / Num. obs: 20514 / % possible obs: 99.2 % / Redundancy: 7.2 % / Biso Wilson estimate: 53.25 Å2 / Rmerge(I) obs: 0.042 / Net I/σ(I): 27.9
Reflection shellResolution: 2.27→2.39 Å / Redundancy: 7.3 % / Rmerge(I) obs: 0.488 / Mean I/σ(I) obs: 4.3 / Num. unique all: 2930 / % possible all: 100

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Processing

Software
NameVersionClassification
CNX2005refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1UKH

1ukh


Resolution: 2.27→27.7 Å / Rfactor Rfree error: 0.009 / Data cutoff high absF: 1131880.99 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.282 1035 5.1 %RANDOM
Rwork0.247 ---
obs0.249 20301 98.9 %-
all-20301 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 64.5533 Å2 / ksol: 0.381814 e/Å3
Displacement parametersBiso mean: 60.2 Å2
Baniso -1Baniso -2Baniso -3
1-0.28 Å20 Å20 Å2
2---4.23 Å20 Å2
3---3.95 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.41 Å0.33 Å
Luzzati d res low-5 Å
Luzzati sigma a0.35 Å0.29 Å
Refinement stepCycle: LAST / Resolution: 2.27→27.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2645 0 42 89 2776
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_angle_deg0.8
X-RAY DIFFRACTIONc_dihedral_angle_d21.9
X-RAY DIFFRACTIONc_improper_angle_d0.65
X-RAY DIFFRACTIONc_mcbond_it1.651.5
X-RAY DIFFRACTIONc_mcangle_it2.792
X-RAY DIFFRACTIONc_scbond_it2.112
X-RAY DIFFRACTIONc_scangle_it3.112.5
Refine LS restraints NCSNCS model details: NONE
LS refinement shellResolution: 2.27→2.41 Å / Rfactor Rfree error: 0.025 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.331 175 5.2 %
Rwork0.304 3180 -
obs--99.9 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.paraprotein.top
X-RAY DIFFRACTION2lig.parlig.top
X-RAY DIFFRACTION3water_rep.paramwater.top
X-RAY DIFFRACTION4ion.paramion.top

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