[English] 日本語
Yorodumi
- PDB-4qp4: Crystal Structure of ERK2 in complex with N-cyclohexyl-9H-purin-6... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4qp4
TitleCrystal Structure of ERK2 in complex with N-cyclohexyl-9H-purin-6-amine
ComponentsMitogen-activated protein kinase 1
Keywordstransferase/transferase inhibitor / Kinase / transferase-transferase inhibitor complex
Function / homology
Function and homology information


phospho-PLA2 pathway / Signaling by MAPK mutants / Suppression of apoptosis / RAF-independent MAPK1/3 activation / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / 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 / Suppression of apoptosis / RAF-independent MAPK1/3 activation / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / 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 / regulation of cellular pH / positive regulation of macrophage proliferation / outer ear morphogenesis / Regulation of the apoptosome activity / regulation of Golgi inheritance / 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 / lung morphogenesis / ERBB2-ERBB3 signaling pathway / response to exogenous dsRNA / regulation of cytoskeleton organization / face development / Activation of the AP-1 family of transcription factors / androgen receptor signaling pathway / ERK/MAPK targets / RUNX2 regulates osteoblast differentiation / pseudopodium / Recycling pathway of L1 / progesterone receptor signaling pathway / positive regulation of telomere capping / MAPK1 (ERK2) activation / negative regulation of cell differentiation / Bergmann glial cell differentiation / thyroid gland development / Advanced glycosylation endproduct receptor signaling / steroid hormone mediated signaling pathway / RHO GTPases Activate NADPH Oxidases / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Regulation of HSF1-mediated heat shock response / regulation of ossification / RHO GTPases Activate WASPs and WAVEs / MAP kinase activity / mitogen-activated protein kinase / phosphatase binding / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / Nuclear events stimulated by ALK signaling in cancer / stress-activated MAPK cascade / Schwann cell development / Growth hormone receptor signaling / lipopolysaccharide-mediated signaling pathway / positive regulation of telomerase activity / ERK1 and ERK2 cascade / cellular response to cadmium ion / cellular response to amino acid starvation / positive regulation of telomere maintenance via telomerase / myelination / NPAS4 regulates expression of target genes / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / ESR-mediated signaling / RNA polymerase II CTD heptapeptide repeat kinase activity / insulin-like growth factor receptor signaling pathway / thymus development / response to nicotine / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription / Signal transduction by L1 / long-term synaptic potentiation / caveola / Negative regulation of FGFR3 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / FCERI mediated MAPK activation / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / FCGR3A-mediated phagocytosis / Negative regulation of FGFR1 signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / B cell receptor signaling pathway / Spry regulation of FGF signaling / peptidyl-threonine phosphorylation / Signaling by high-kinase activity BRAF mutants / regulation of protein stability / MAP2K and MAPK activation / Oncogene Induced Senescence / mitotic spindle / Regulation of actin dynamics for phagocytic cup formation
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 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase 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 / 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, 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
N-cyclohexyl-9H-purin-6-amine / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsYin, J. / Wang, W.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2015
Title: Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors.
Authors: Burdick, D.J. / Wang, S. / Heise, C. / Pan, B. / Drummond, J. / Yin, J. / Goeser, L. / Magnuson, S. / Blaney, J. / Moffat, J. / Wang, W. / Chen, H.
History
DepositionJun 22, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 23, 2015Provider: repository / Type: Initial release
Revision 1.1Dec 16, 2015Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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

-
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)85,5324
Polymers85,0982
Non-polymers4352
Water5,495305
1
A: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,7662
Polymers42,5491
Non-polymers2171
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Mitogen-activated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,7662
Polymers42,5491
Non-polymers2171
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)59.428, 67.229, 86.997
Angle α, β, γ (deg.)90.00, 102.21, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#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: 42548.855 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK1, ERK2, PRKM1, PRKM2 / Production host: Escherichia coli (E. coli)
References: UniProt: P28482, mitogen-activated protein kinase
#2: Chemical ChemComp-36O / N-cyclohexyl-9H-purin-6-amine


Mass: 217.270 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C11H15N5
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 305 / 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 Å3/Da / Density % sol: 38.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 10% PEG3350, 0.2 M proline, and 0.1 M HEPES pH7.5, in a 24-well Linbro plates incubated at 4C, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 6, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. all: 34166 / Num. obs: 33654 / % possible obs: 98.5 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2

-
Processing

Software
NameVersionClassification
HKL-2000data collection
PHASERphasing
PHENIX(phenix.refine: 1.8.2_1309)refinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.2→28.466 Å / SU ML: 0.25 / σ(F): 1.35 / Phase error: 25.13 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2352 1679 4.99 %
Rwork0.1866 --
obs0.1891 33629 98.31 %
all-34166 -
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.2→28.466 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5492 0 32 305 5829
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0045690
X-RAY DIFFRACTIONf_angle_d0.8097702
X-RAY DIFFRACTIONf_dihedral_angle_d13.6342146
X-RAY DIFFRACTIONf_chiral_restr0.06844
X-RAY DIFFRACTIONf_plane_restr0.004982
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1999-2.26470.32891350.26012586X-RAY DIFFRACTION97
2.2647-2.33770.27541270.23092697X-RAY DIFFRACTION100
2.3377-2.42120.26281280.20862713X-RAY DIFFRACTION100
2.4212-2.51810.2641400.19872637X-RAY DIFFRACTION100
2.5181-2.63260.26691460.20732718X-RAY DIFFRACTION99
2.6326-2.77130.25251420.19872646X-RAY DIFFRACTION99
2.7713-2.94480.27791480.20322657X-RAY DIFFRACTION99
2.9448-3.17190.25361430.19742682X-RAY DIFFRACTION99
3.1719-3.49060.21631390.18762681X-RAY DIFFRACTION98
3.4906-3.99450.19861450.16492650X-RAY DIFFRACTION98
3.9945-5.02810.22371520.15352642X-RAY DIFFRACTION97
5.0281-28.46860.19821340.17872641X-RAY DIFFRACTION95
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.89460.42840.42080.83260.08121.2508-0.01340.0566-0.03580.03060.11050.02630.2813-0.065100.26910.0342-0.00620.28120.02180.224.2615-13.94876.4155
20.78740.13760.5131.0212-0.38291.4104-0.0332-0.00010.0239-0.0428-0.0188-0.0198-0.0724-0.01290.00010.18580.00930.03140.134-0.00160.165825.7447-0.87616.8464
30.9662-0.19620.19661.0862-0.93340.8639-0.02910.088-0.06-0.2051-0.0723-0.13510.18690.1797-0.00010.20370.03040.01150.27370.01960.243945.9877-47.979836.0936
40.77330.19960.09151.44750.32941.2198-0.0527-0.0258-0.0213-0.1479-0.0626-0.02710.00920.0391-0.00440.16540.01610.00510.1420.00880.155924.3904-33.646226.5025
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND ( RESID 13:108 OR RESID 335:357 ) )A13 - 108
2X-RAY DIFFRACTION1( CHAIN A AND ( RESID 13:108 OR RESID 335:357 ) )A335 - 357
3X-RAY DIFFRACTION2( CHAIN A AND RESID 109:334 )A109 - 334
4X-RAY DIFFRACTION3( CHAIN B AND ( RESID 12:108 OR RESID 335:357 ) )B12 - 108
5X-RAY DIFFRACTION3( CHAIN B AND ( RESID 12:108 OR RESID 335:357 ) )B335 - 357
6X-RAY DIFFRACTION4( CHAIN B AND RESID 109:334 )B109 - 334

+
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