[English] 日本語
Yorodumi
- PDB-7w5o: Crystal structure of ERK2 with an allosteric inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7w5o
TitleCrystal structure of ERK2 with an allosteric inhibitor
ComponentsMitogen-activated protein kinase 1
KeywordsTRANSFERASE / protein kinase / allosteric inhibitor / activation loop
Function / homology
Function and homology information


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 / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / ERKs are inactivated ...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 / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / ERKs are inactivated / response to epidermal growth factor / Signaling by MAP2K mutants / Signaling by NODAL / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / positive regulation of macrophage proliferation / Regulation of the apoptosome activity / regulation of cellular pH / outer ear morphogenesis / regulation of Golgi inheritance / Signaling by LTK in cancer / ERBB signaling pathway / labyrinthine layer blood vessel development / mammary gland epithelial cell proliferation / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / IFNG signaling activates MAPKs / Frs2-mediated activation / positive regulation of macrophage chemotaxis / positive regulation of telomere maintenance / ERBB2-ERBB3 signaling pathway / lung morphogenesis / regulation of cytoskeleton organization / ERK/MAPK targets / Activation of the AP-1 family of transcription factors / face development / response to exogenous dsRNA / RUNX2 regulates osteoblast differentiation / Recycling pathway of L1 / pseudopodium / MAPK1 (ERK2) activation / Bergmann glial cell differentiation / thyroid gland development / androgen receptor signaling pathway / Advanced glycosylation endproduct receptor signaling / steroid hormone receptor signaling pathway / negative regulation of cell differentiation / MAP kinase activity / RHO GTPases Activate NADPH Oxidases / regulation of ossification / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Regulation of HSF1-mediated heat shock response / RHO GTPases Activate WASPs and WAVEs / mitogen-activated protein kinase / phosphatase binding / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / progesterone receptor signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / Schwann cell development / Growth hormone receptor signaling / Nuclear events stimulated by ALK signaling in cancer / stress-activated MAPK cascade / lipopolysaccharide-mediated signaling pathway / NPAS4 regulates expression of target genes / phosphotyrosine residue binding / myelination / NCAM signaling for neurite out-growth / ERK1 and ERK2 cascade / positive regulation of peptidyl-threonine phosphorylation / RNA polymerase II CTD heptapeptide repeat kinase activity / ESR-mediated signaling / cellular response to amino acid starvation / insulin-like growth factor receptor signaling pathway / thymus development / Regulation of PTEN gene transcription / Signal transduction by L1 / positive regulation of cholesterol biosynthetic process / FCERI mediated MAPK activation / B cell receptor signaling pathway / FCGR3A-mediated phagocytosis / response to nicotine / peptidyl-threonine phosphorylation / Negative regulation of FGFR3 signaling / long-term synaptic potentiation / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Negative regulation of FGFR1 signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / regulation of protein stability / Oncogene Induced Senescence / caveola / Regulation of actin dynamics for phagocytic cup formation / mitotic spindle
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
Chem-5ID / Chem-6GI / MALONIC ACID / SUCCINIC ACID / D(-)-TARTARIC ACID / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 Å
AuthorsYoshida, M. / Kinoshita, T.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Biochem.Biophys.Res.Commun. / Year: 2022
Title: Identification of a novel target site for ATP-independent ERK2 inhibitors.
Authors: Yoshida, M. / Nagao, H. / Sugiyama, H. / Sawa, M. / Kinoshita, T.
History
DepositionNov 30, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Feb 23, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 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
B: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)87,00516
Polymers84,6212
Non-polymers2,38414
Water2,144119
1
A: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,5129
Polymers42,3101
Non-polymers1,2028
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area110 Å2
ΔGint-7 kcal/mol
Surface area16700 Å2
MethodPISA
2
B: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,4927
Polymers42,3101
Non-polymers1,1826
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area16030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.812, 82.812, 274.440
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212
Space group name HallP4abw2nw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+1/4
#3: y+1/2,-x+1/2,z+3/4
#4: x+1/2,-y+1/2,-z+3/4
#5: -x+1/2,y+1/2,-z+1/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2

-
Components

-
Protein , 1 types, 2 molecules AB

#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: 42310.410 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK1, ERK2, PRKM1, PRKM2 / Plasmid: pGEX6p-1 / Production host: Escherichia coli BL21 (bacteria)
References: UniProt: P28482, mitogen-activated protein kinase

-
Non-polymers , 8 types, 133 molecules

#2: Chemical ChemComp-5ID / (2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL / 5-IODOTUBERCIDIN


Mass: 392.150 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H13IN4O4
#3: Chemical
ChemComp-MLA / MALONIC ACID / DICARBOXYLIC ACID C3 / PROPANEDIOLIC ACID / METHANEDICARBOXYLIC ACID


Mass: 104.061 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H4O4
#4: Chemical ChemComp-SIN / SUCCINIC ACID


Mass: 118.088 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C4H6O4
#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Chemical ChemComp-EPE / 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES


Mass: 238.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H18N2O4S / Comment: pH buffer*YM
#7: Chemical ChemComp-TAR / D(-)-TARTARIC ACID


Mass: 150.087 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H6O6
#8: Chemical ChemComp-6GI / 13-[4-({Imidazo[1,2-a]pyridin-2-yl}methoxy)phenyl]-4,8-dioxa-12,14,16,18-tetraazatetracyclo[9.7.0.0^{3,9}.0^{12,17}]octadeca-1(11),2,9,15,17-pentaen-15-amine


Mass: 481.506 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H23N7O3
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 119 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.78 Å3/Da / Density % sol: 55.74 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7 / Details: Tacsimate, HEPES, PEGMME5000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL44XU / Wavelength: 0.9 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 4, 2020
RadiationMonochromator: mirrrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 2.35→49.32 Å / Num. obs: 46821 / % possible obs: 99.8 % / Redundancy: 13.2 % / Biso Wilson estimate: 55.87 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.179 / Net I/σ(I): 99.9
Reflection shellResolution: 2.35→2.43 Å / Num. unique obs: 40848 / CC1/2: 0.62 / % possible all: 99.43

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
PHENIX1.19.2_4158refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4qp1

4qp1


Resolution: 2.35→49.32 Å / SU ML: 0.3648 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 31.559
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2788 1749 4.28 %
Rwork0.2254 39091 -
obs0.2276 40840 99.83 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 68.79 Å2
Refinement stepCycle: LAST / Resolution: 2.35→49.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5699 0 155 119 5973
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00975990
X-RAY DIFFRACTIONf_angle_d1.08688119
X-RAY DIFFRACTIONf_chiral_restr0.059873
X-RAY DIFFRACTIONf_plane_restr0.00991039
X-RAY DIFFRACTIONf_dihedral_angle_d23.7082259
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.35-2.420.39481400.34613140X-RAY DIFFRACTION99.42
2.42-2.50.36281440.30993205X-RAY DIFFRACTION99.82
2.5-2.590.33241440.2983223X-RAY DIFFRACTION99.85
2.59-2.690.34981420.2833180X-RAY DIFFRACTION99.79
2.69-2.810.32331430.28163198X-RAY DIFFRACTION99.79
2.81-2.960.3741460.27343228X-RAY DIFFRACTION99.73
2.96-3.150.34791420.25913215X-RAY DIFFRACTION99.79
3.15-3.390.271450.24143239X-RAY DIFFRACTION100
3.39-3.730.3141470.2283280X-RAY DIFFRACTION99.94
3.73-4.270.24981470.19473290X-RAY DIFFRACTION100
4.27-5.380.23291500.18993339X-RAY DIFFRACTION99.97
5.38-49.320.24421590.20453554X-RAY DIFFRACTION99.89

+
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