[English] 日本語
Yorodumi
- PDB-6nbs: WT ERK2 with compound 2507-8 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6nbs
TitleWT ERK2 with compound 2507-8
ComponentsMitogen-activated protein kinase 1
KeywordsTransferase/Transferase Inhibitor / Inhibitor / MAPK / Transferase-Transferase Inhibitor complex
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 / phospho-PLA2 pathway / Signaling by MAPK mutants / RAF-independent MAPK1/3 activation / Suppression of apoptosis / Gastrin-CREB signalling pathway via PKC and MAPK / Signaling by Activin / cellular response to toxic substance / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / Signaling by MAP2K mutants / Signaling by NODAL / ERKs are inactivated / mitogen-activated protein kinase kinase kinase binding / cellular response to methionine / response to epidermal growth factor / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / Regulation of the apoptosome activity / positive regulation of macrophage proliferation / response to alcohol / regulation of cellular pH / outer ear morphogenesis / Signaling by LTK in cancer / 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 / Negative feedback regulation of MAPK pathway / positive regulation of peptidyl-threonine phosphorylation / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / IFNG signaling activates MAPKs / cellular response to insulin-like growth factor stimulus / Frs2-mediated activation / ERBB2-ERBB3 signaling pathway / MAPK1 (ERK2) activation / positive regulation of macrophage chemotaxis / Activation of the AP-1 family of transcription factors / regulation of cytoskeleton organization / ERK/MAPK targets / RUNX2 regulates osteoblast differentiation / response to exogenous dsRNA / face development / lung morphogenesis / positive regulation of telomere maintenance / response to testosterone / Recycling pathway of L1 / pseudopodium / Bergmann glial cell differentiation / androgen receptor signaling pathway / thyroid gland development / steroid hormone receptor signaling pathway
Similarity search - Function
Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / 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 ...Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-KJ4 / (5S)-5-benzyl-4,5-dihydro-1H-imidazol-2-amine / Mitogen-activated protein kinase 1 / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsSammons, R.M. / Perry, N.A. / Cho, E.J. / Kaoud, T.S. / Zamora-Olivares, D.P. / Piserchio, A. / Houghten, R.A. / Giulianotti, M. / Li, Y. / Debevec, G. ...Sammons, R.M. / Perry, N.A. / Cho, E.J. / Kaoud, T.S. / Zamora-Olivares, D.P. / Piserchio, A. / Houghten, R.A. / Giulianotti, M. / Li, Y. / Debevec, G. / Gurevich, V.V. / Ghose, R. / Iverson, T.M. / Dalby, K.N.
Funding support United States, 2items
OrganizationGrant numberCountry
American Heart Association16PRE30180007 United States
American Heart Association18PRE34030017 United States
CitationJournal: Acs Chem.Biol. / Year: 2019
Title: A Novel Class of Common Docking Domain Inhibitors That Prevent ERK2 Activation and Substrate Phosphorylation.
Authors: Sammons, R.M. / Perry, N.A. / Li, Y. / Cho, E.J. / Piserchio, A. / Zamora-Olivares, D.P. / Ghose, R. / Kaoud, T.S. / Debevec, G. / Bartholomeusz, C. / Gurevich, V.V. / Iverson, T.M. / ...Authors: Sammons, R.M. / Perry, N.A. / Li, Y. / Cho, E.J. / Piserchio, A. / Zamora-Olivares, D.P. / Ghose, R. / Kaoud, T.S. / Debevec, G. / Bartholomeusz, C. / Gurevich, V.V. / Iverson, T.M. / Giulianotti, M. / Houghten, R.A. / Dalby, K.N.
History
DepositionDec 10, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 31, 2019Provider: repository / Type: Initial release
Revision 1.1Aug 12, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Sep 8, 2021Group: Database references / Source and taxonomy / Structure summary
Category: database_2 / entity_name_com ...database_2 / entity_name_com / entity_src_gen / struct_ref / struct_ref_seq / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_name_com.name / _entity_src_gen.gene_src_common_name / _entity_src_gen.pdbx_gene_src_gene / _entity_src_gen.pdbx_gene_src_ncbi_taxonomy_id / _entity_src_gen.pdbx_gene_src_scientific_name / _struct_ref.db_code / _struct_ref.pdbx_align_begin / _struct_ref.pdbx_db_accession / _struct_ref.pdbx_seq_one_letter_code / _struct_ref_seq.db_align_beg / _struct_ref_seq.db_align_end / _struct_ref_seq.pdbx_auth_seq_align_beg / _struct_ref_seq.pdbx_db_accession / _struct_ref_seq.seq_align_beg
Revision 1.3Oct 11, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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)43,2715
Polymers42,4331
Non-polymers8384
Water3,747208
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: NMR analysis performed on the inhibitor to show assembly
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)48.895, 71.242, 60.167
Angle α, β, γ (deg.)90.00, 109.37, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 1 molecules A

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


Mass: 42432.777 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, UniProt: P28482*PLUS, mitogen-activated protein kinase

-
Non-polymers , 5 types, 212 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-KJ7 / (5S)-5-benzyl-4,5-dihydro-1H-imidazol-2-amine


Mass: 175.230 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H13N3
#5: Chemical ChemComp-KJ4 / N-{3-[(2Z,4S)-1-(2-{[2-(2-amino-1H-imidazol-1-yl)ethyl](methyl)amino}ethyl)-3-(3-cyclohexylpropyl)-2-iminoimidazolidin-4-yl]propyl}guanidine


Mass: 474.689 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H46N10
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 208 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.33 Å3/Da / Density % sol: 47.21 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop
Details: 33% PEG 5,000 MME, 0.25 M ammonium sulfate, 0.1 M MES, pH 6.5

-
Data collection

DiffractionMean temperature: 446.15 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.9798 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 23, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9798 Å / Relative weight: 1
ReflectionResolution: 1.9→38.72 Å / Num. obs: 30765 / % possible obs: 99.9 % / Redundancy: 4.5 % / Biso Wilson estimate: 22.6 Å2 / Rmerge(I) obs: 0.076 / Rsym value: 0.076 / Net I/σ(I): 35.057
Reflection shellResolution: 1.9→1.93 Å / Redundancy: 4.5 % / Rmerge(I) obs: 0.565 / Mean I/σ(I) obs: 5.015 / CC1/2: 0.607 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX(1.14_3211: ???)refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1ERK

1erk
PDB Unreleased entry


Resolution: 1.9→38.72 Å / SU ML: 0.18 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.5
RfactorNum. reflection% reflection
Rfree0.2218 1424 4.64 %
Rwork0.1801 --
obs0.182 30668 99.63 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.9→38.72 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2791 0 58 208 3057
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072946
X-RAY DIFFRACTIONf_angle_d0.8223993
X-RAY DIFFRACTIONf_dihedral_angle_d4.6112481
X-RAY DIFFRACTIONf_chiral_restr0.054434
X-RAY DIFFRACTIONf_plane_restr0.005510
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9003-1.96820.26271260.20992833X-RAY DIFFRACTION97
1.9682-2.0470.22641490.19942916X-RAY DIFFRACTION100
2.047-2.14020.30341410.19032928X-RAY DIFFRACTION100
2.1402-2.2530.26231400.19152910X-RAY DIFFRACTION100
2.253-2.39410.23171360.18862950X-RAY DIFFRACTION100
2.3941-2.5790.23011510.18252917X-RAY DIFFRACTION100
2.579-2.83840.25031490.19132912X-RAY DIFFRACTION100
2.8384-3.2490.23671360.18222952X-RAY DIFFRACTION100
3.249-4.09260.20251450.16522947X-RAY DIFFRACTION100
4.0926-38.72830.18241510.16972979X-RAY DIFFRACTION100

+
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