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- PDB-8qrb: Crystal structure of ERK2 in complex with a covalently bound macr... -

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Basic information

Entry
Database: PDB / ID: 8qrb
TitleCrystal structure of ERK2 in complex with a covalently bound macrocyclic ligand
ComponentsMitogen-activated protein kinase 1
KeywordsSIGNALING PROTEIN / SERINE/THREONINE-PROTEIN KINASE
Function / homology
Function and homology information


phospho-PLA2 pathway / RAF-independent MAPK1/3 activation / MAPK1 (ERK2) activation / Signaling by NODAL / Frs2-mediated activation / ERK/MAPK targets / ERKs are inactivated / Activation of the AP-1 family of transcription factors / Transcriptional and post-translational regulation of MITF-M expression and activity / Negative feedback regulation of MAPK pathway ...phospho-PLA2 pathway / RAF-independent MAPK1/3 activation / MAPK1 (ERK2) activation / Signaling by NODAL / Frs2-mediated activation / ERK/MAPK targets / ERKs are inactivated / Activation of the AP-1 family of transcription factors / Transcriptional and post-translational regulation of MITF-M expression and activity / Negative feedback regulation of MAPK pathway / Gastrin-CREB signalling pathway via PKC and MAPK / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / IFNG signaling activates MAPKs / Golgi Cisternae Pericentriolar Stack Reorganization / RHO GTPases Activate WASPs and WAVEs / Estrogen-stimulated signaling through PRKCZ / Growth hormone receptor signaling / Spry regulation of FGF signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Oxidative Stress Induced Senescence / Senescence-Associated Secretory Phenotype (SASP) / Oncogene Induced Senescence / Regulation of actin dynamics for phagocytic cup formation / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Signal attenuation / NCAM signaling for neurite out-growth / Negative regulation of FGFR1 signaling / Negative regulation of FGFR3 signaling / Negative regulation of FGFR4 signaling / Regulation of the apoptosome activity / Signaling by Activin / Negative regulation of FGFR2 signaling / Signal transduction by L1 / RHO GTPases Activate NADPH Oxidases / Negative regulation of MAPK pathway / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interferon gamma signaling / FCERI mediated MAPK activation / Regulation of HSF1-mediated heat shock response / diadenosine tetraphosphate biosynthetic process / MAP2K and MAPK activation / neural crest cell development / Recycling pathway of L1 / cellular response to toxic substance / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / mitogen-activated protein kinase kinase kinase binding / cellular response to methionine / response to epidermal growth factor / positive regulation of macrophage proliferation / response to alcohol / regulation of cellular pH / outer ear morphogenesis / regulation of Golgi inheritance / labyrinthine layer blood vessel development / RAF/MAP kinase cascade / Thrombin signalling through proteinase activated receptors (PARs) / ERBB signaling pathway / Neutrophil degranulation / mammary gland epithelial cell proliferation / trachea formation / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / cellular response to insulin-like growth factor stimulus / ERBB2-ERBB3 signaling pathway / positive regulation of macrophage chemotaxis / regulation of cytoskeleton organization / response to exogenous dsRNA / face development / lung morphogenesis / positive regulation of telomere maintenance / response to testosterone / pseudopodium / Bergmann glial cell differentiation / androgen receptor signaling pathway / thyroid gland development / steroid hormone receptor signaling pathway / decidualization / MAP kinase activity / negative regulation of cell differentiation / regulation of ossification / JUN kinase activity / mitogen-activated protein kinase / phosphatase binding / Schwann cell development / progesterone receptor signaling pathway / stress-activated MAPK cascade / estrous cycle / positive regulation of cardiac muscle cell proliferation / cellular response to platelet-derived growth factor stimulus / cellular response to cAMP / sensory perception of pain / dendrite cytoplasm / phosphotyrosine residue binding / myelination / RNA polymerase II CTD heptapeptide repeat kinase activity / peptidyl-threonine phosphorylation / ERK1 and ERK2 cascade / cellular response to epidermal growth factor stimulus
Similarity search - Function
Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. ...Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.51 Å
AuthorsGelin, M. / Labesse, G.
Funding support France, 1items
OrganizationGrant numberCountry
Agence Nationale de la Recherche (ANR)ANR-20-CE18-0025 France
Citation
Journal: To Be Published
Title: Crystal structure of ERK2 in complex with a covalently bound macrocyclic ligand
Authors: Gelin, M. / Labesse, G. / Guichou, J.-F. / Pons, J.-L. / Barluenga, S. / Katickeyan, G. / Winssinger, N.
#1: Journal: Acta Crystallogr., Sect. D: Biol. Crystallogr. / Year: 2012
Title: Towards automated crystallographic structure refinement with phenix.refine.
Authors: Afonine, P.V.
History
DepositionOct 6, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 16, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,0307
Polymers42,2361
Non-polymers7956
Water6,395355
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: SAXS, monomer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1100 Å2
ΔGint-17 kcal/mol
Surface area16530 Å2
Unit cell
Length a, b, c (Å)48.810, 70.730, 60.420
Angle α, β, γ (deg.)90.000, 109.320, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

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Components

#1: Protein Mitogen-activated protein kinase 1


Mass: 42235.547 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Mapk1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P63086
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-WLZ / (4~{S},7~{R},9~{S},10~{S},12~{E})-7-fluoranyl-4-methyl-9,10,16,18-tetrakis(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),12,15,17-tetraene-2,8-dione


Mass: 368.354 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H21FO7 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 355 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
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: 2.33 Å3/Da / Density % sol: 47.22 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop
Details: PEG MME 2000, 0.1M MES pH 6.5, 0.1M ammonium sulfate, 0.02M beta-mercaptoethanol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.8726 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Dec 11, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8726 Å / Relative weight: 1
ReflectionResolution: 1.51→26.44 Å / Num. obs: 60803 / % possible obs: 99.9 % / Redundancy: 3.9 % / Biso Wilson estimate: 16.31 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.093 / Rpim(I) all: 0.053 / Rrim(I) all: 0.107 / Χ2: 1.02 / Net I/σ(I): 9.1 / Num. measured all: 240042
Reflection shellResolution: 1.51→1.54 Å / % possible obs: 100 % / Redundancy: 3.9 % / Rmerge(I) obs: 0.835 / Num. measured all: 11671 / Num. unique obs: 2995 / CC1/2: 0.599 / Rpim(I) all: 0.489 / Rrim(I) all: 0.97 / Χ2: 0.94 / Net I/σ(I) obs: 2

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
Aimlessdata scaling
MOSFLMdata reduction
PHENIXphasing
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.51→23.37 Å / SU ML: 0.1728 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.6028
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2093 2888 4.75 %
Rwork0.1767 57884 -
obs0.1782 60772 99.94 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 24.07 Å2
Refinement stepCycle: LAST / Resolution: 1.51→23.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2851 0 48 355 3254
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00483118
X-RAY DIFFRACTIONf_angle_d0.88754239
X-RAY DIFFRACTIONf_chiral_restr0.0594468
X-RAY DIFFRACTIONf_plane_restr0.012535
X-RAY DIFFRACTIONf_dihedral_angle_d6.6986431
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.51-1.530.3131520.27362718X-RAY DIFFRACTION99.97
1.53-1.560.32131280.25492761X-RAY DIFFRACTION100
1.56-1.590.27531370.24262740X-RAY DIFFRACTION99.97
1.59-1.620.27621370.23082733X-RAY DIFFRACTION100
1.62-1.650.2741550.21742738X-RAY DIFFRACTION100
1.65-1.690.25781360.21232775X-RAY DIFFRACTION100
1.69-1.730.2331520.19822735X-RAY DIFFRACTION100
1.73-1.770.21381420.19542712X-RAY DIFFRACTION100
1.77-1.820.23451310.18792775X-RAY DIFFRACTION100
1.82-1.870.25991140.19322782X-RAY DIFFRACTION99.97
1.87-1.930.22471230.17962731X-RAY DIFFRACTION99.96
1.93-20.23771280.17692759X-RAY DIFFRACTION100
2-2.080.18881410.16792771X-RAY DIFFRACTION100
2.08-2.180.20281490.16682716X-RAY DIFFRACTION99.97
2.18-2.290.19971360.16422783X-RAY DIFFRACTION100
2.29-2.440.22891370.16832774X-RAY DIFFRACTION100
2.44-2.620.20811420.17472741X-RAY DIFFRACTION100
2.62-2.890.19331610.16552749X-RAY DIFFRACTION99.93
2.89-3.30.20661290.16922784X-RAY DIFFRACTION99.97
3.3-4.160.16881290.15212778X-RAY DIFFRACTION100
4.16-23.370.18321290.17352829X-RAY DIFFRACTION99.13

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