[English] 日本語
Yorodumi
- PDB-4xrj: Crystal structure of ERK2 in complex with an inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xrj
TitleCrystal structure of ERK2 in complex with an inhibitor
ComponentsMitogen-activated protein kinase 1
KeywordsAPOPTOSIS / serine threonine kinase inhibitor
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 / positive regulation of telomere maintenance / lung morphogenesis / response to testosterone / pseudopodium / Bergmann glial cell differentiation / androgen receptor signaling pathway / thyroid gland development / steroid hormone receptor signaling pathway / decidualization / negative regulation of cell differentiation / MAP kinase activity / 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. / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. ...Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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, ATP binding site / Protein kinases ATP-binding region signature. / 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-620 / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.69 Å
AuthorsGelin, M. / Allemand, F. / Labesse, G. / Guichou, J.F.
CitationJournal: Acta Crystallogr.,Sect.D / Year: 2015
Title: Combining `dry' co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography.
Authors: Gelin, M. / Delfosse, V. / Allemand, F. / Hoh, F. / Sallaz-Damaz, Y. / Pirocchi, M. / Bourguet, W. / Ferrer, J.L. / Labesse, G. / Guichou, J.F.
History
DepositionJan 21, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Aug 12, 2015Provider: repository / Type: Initial release
Revision 1.1Aug 19, 2015Group: Database references
Revision 1.2Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)40,7963
Polymers40,4041
Non-polymers3922
Water2,900161
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area190 Å2
ΔGint-13 kcal/mol
Surface area16890 Å2
MethodPISA
Unit cell
Length a, b, c (Å)49.155, 71.480, 60.760
Angle α, β, γ (deg.)90.000, 108.700, 90.000
Int Tables number4
Space group name H-MP1211
Detailsbiological unit is the same as asym.

-
Components

#1: Protein Mitogen-activated protein kinase 1 / MAPK 1 / ERT1 / Extracellular signal-regulated kinase 2 / ERK-2 / MAP kinase isoform p42 / p42-MAPK ...MAPK 1 / ERT1 / Extracellular signal-regulated kinase 2 / ERK-2 / MAP kinase isoform p42 / p42-MAPK / Mitogen-activated protein kinase 2 / MAPK 2


Mass: 40403.582 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Mapk1, Erk2, Mapk, Prkm1 / Production host: Escherichia coli (E. coli)
References: UniProt: P63086, mitogen-activated protein kinase
#2: Chemical ChemComp-620 / N~1~-[3-(benzyloxy)benzyl]-1H-tetrazole-1,5-diamine


Mass: 296.327 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H16N6O
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 161 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 50.85 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: MES 100mM pH 6.5, (NH4)2SO4 200mM, beta-mercaptoethanol 20mM and 26% (w/v) PEG MME2000

-
Data collection

DiffractionMean temperature: 298 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: BM30A / Wavelength: 0.9797 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 3, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9797 Å / Relative weight: 1
ReflectionResolution: 1.69→44.8 Å / Num. obs: 39592 / % possible obs: 93 % / Redundancy: 3 % / Net I/σ(I): 3.6

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
PDB_EXTRACT3.15data extraction
SCALAdata scaling
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.69→44.8 Å / Cor.coef. Fo:Fc: 0.974 / Cor.coef. Fo:Fc free: 0.961 / SU B: 3.565 / SU ML: 0.054 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.128 / ESU R Free: 0.09 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.18 2088 5 %RANDOM
Rwork0.1359 39592 --
obs0.1381 39592 92.88 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 90.53 Å2 / Biso mean: 27.652 Å2 / Biso min: 9 Å2
Baniso -1Baniso -2Baniso -3
1--0.26 Å20 Å2-0.42 Å2
2--0.31 Å2-0 Å2
3---0.08 Å2
Refinement stepCycle: final / Resolution: 1.69→44.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2839 0 27 161 3027
Biso mean--27.85 34.95 -
Num. residues----346
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0193104
X-RAY DIFFRACTIONr_bond_other_d0.0020.023025
X-RAY DIFFRACTIONr_angle_refined_deg1.4561.994244
X-RAY DIFFRACTIONr_angle_other_deg0.8983.0027001
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6035393
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.56924.342152
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.92115570
X-RAY DIFFRACTIONr_dihedral_angle_4_deg25.5251519
X-RAY DIFFRACTIONr_chiral_restr0.0930.2469
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0213499
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02721
X-RAY DIFFRACTIONr_mcbond_it3.3552.3731435
X-RAY DIFFRACTIONr_mcbond_other3.332.371434
X-RAY DIFFRACTIONr_mcangle_it4.0753.5711805
X-RAY DIFFRACTIONr_rigid_bond_restr3.61836129
X-RAY DIFFRACTIONr_sphericity_free26.337553
X-RAY DIFFRACTIONr_sphericity_bonded11.44956140
LS refinement shellResolution: 1.687→1.731 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.256 138 -
Rwork0.216 2846 -
all-2984 -
obs--90.98 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more