[English] 日本語
Yorodumi
- PDB-8pt0: ERK2 covelently bound to RU75 cyclohexenone based inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8pt0
TitleERK2 covelently bound to RU75 cyclohexenone based inhibitor
ComponentsMitogen-activated protein kinase 1
KeywordsSIGNALING PROTEIN / MAPK kinase / MAPK / inhibitor / covalent / ERK2 / Michael acceptor warhead
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 / response to epidermal growth factor ...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 / response to epidermal growth factor / ERKs are inactivated / Signaling by MAP2K mutants / Signaling by NODAL / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / positive regulation of macrophage proliferation / Regulation of the apoptosome activity / outer ear morphogenesis / regulation of cellular pH / 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 / ERBB2-ERBB3 signaling pathway / lung morphogenesis / response to exogenous dsRNA / Activation of the AP-1 family of transcription factors / ERK/MAPK targets / regulation of cytoskeleton organization / face development / androgen receptor signaling pathway / pseudopodium / RUNX2 regulates osteoblast differentiation / : / positive regulation of telomere capping / Recycling pathway of L1 / MAPK1 (ERK2) activation / Bergmann glial cell differentiation / thyroid gland development / negative regulation of cell differentiation / Advanced glycosylation endproduct receptor signaling / steroid hormone receptor signaling pathway / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / Regulation of HSF1-mediated heat shock response / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / mitogen-activated protein kinase / RHO GTPases Activate WASPs and WAVEs / phosphatase binding / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / Transcriptional and post-translational regulation of MITF-M expression and activity / progesterone receptor signaling pathway / Schwann cell development / Nuclear events stimulated by ALK signaling in cancer / Growth hormone receptor signaling / lipopolysaccharide-mediated signaling pathway / stress-activated MAPK cascade / positive regulation of telomere maintenance via telomerase / phosphotyrosine residue binding / NPAS4 regulates expression of target genes / cellular response to cadmium ion / myelination / ERK1 and ERK2 cascade / cellular response to amino acid starvation / NCAM signaling for neurite out-growth / ESR-mediated signaling / RNA polymerase II CTD heptapeptide repeat kinase activity / insulin-like growth factor receptor signaling pathway / thymus development / positive regulation of peptidyl-threonine phosphorylation / Signal transduction by L1 / Regulation of PTEN gene transcription / long-term synaptic potentiation / response to nicotine / peptidyl-threonine phosphorylation / Negative regulation of FGFR2 signaling / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / Negative regulation of FGFR3 signaling / B cell receptor signaling pathway / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Negative regulation of FGFR4 signaling / 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 / caveola / Oncogene Induced Senescence
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
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / : / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.65 Å
AuthorsSok, P. / Poti, A. / Remenyi, A. / Gogl, G.
Funding support Hungary, 1items
OrganizationGrant numberCountry
National Research Development and Innovation Office (NKFIH)KKP 126963 Hungary
CitationJournal: Nat Commun / Year: 2024
Title: Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.
Authors: Poti, A.L. / Balint, D. / Alexa, A. / Sok, P. / Ozsvath, K. / Albert, K. / Turczel, G. / Magyari, S. / Ember, O. / Papp, K. / Kiraly, S.B. / Imre, T. / Nemeth, K. / Kurtan, T. / Gogl, G. / ...Authors: Poti, A.L. / Balint, D. / Alexa, A. / Sok, P. / Ozsvath, K. / Albert, K. / Turczel, G. / Magyari, S. / Ember, O. / Papp, K. / Kiraly, S.B. / Imre, T. / Nemeth, K. / Kurtan, T. / Gogl, G. / Varga, S. / Soos, T. / Remenyi, A.
History
DepositionJul 13, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 24, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Database references / Structure summary
Category: citation / citation_author ...citation / citation_author / pdbx_entry_details / pdbx_modification_feature
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 / _pdbx_entry_details.has_protein_modification

-
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)42,6504
Polymers41,7471
Non-polymers9033
Water5,350297
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1180 Å2
ΔGint-4 kcal/mol
Surface area16010 Å2
MethodPISA
Unit cell
Length a, b, c (Å)41.490, 77.050, 123.390
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
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: 41746.941 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: The dephosphorylated inactive ERK2 kinase with RU75 covalent inhibitor at the docking groove
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK1, ERK2, PRKM1, PRKM2 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P28482, mitogen-activated protein kinase
#2: Chemical ChemComp-ANP / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER


Mass: 506.196 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H17N6O12P3 / Comment: AMP-PNP, energy-carrying molecule analogue*YM
#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-EAI / ~{O}1-methyl ~{O}3-(phenylmethyl) (1~{R},3~{S})-1-methyl-4-oxidanylidene-cyclohexane-1,3-dicarboxylate


Mass: 304.338 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H20O5 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 297 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.41 Å3/Da / Density % sol: 49 % / Description: rhomboid
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 30% PEG3350, 0.1 M Tris pH 8.5.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 17, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.65→38.52 Å / Num. obs: 48499 / % possible obs: 100 % / Redundancy: 12.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.093 / Rrim(I) all: 0.097 / Net I/σ(I): 13.99
Reflection shell
Resolution (Å)Rmerge(I) obsNum. unique obsCC1/2Rrim(I) allDiffraction-ID
1.65-1.691.35735150.7181.4151
1.69-1.741.0634750.8441.1051
1.74-1.790.85833380.8740.8941
1.79-1.840.64732520.9260.6741
1.84-1.910.49831690.9540.5191
1.91-1.970.38430800.9740.41
1.97-2.050.2929370.9820.3031
2.05-2.130.22928640.9850.2391
2.13-2.220.19127400.9920.1991
2.22-2.330.15826250.9920.1651
2.33-2.460.13925160.9950.1451
2.46-2.610.12223710.9950.1271
2.61-2.790.09822280.9970.1031
2.79-3.010.08520990.9970.0891
3.01-3.30.07219140.9980.0761
3.3-3.690.06117730.9980.0641
3.69-4.260.05515630.9980.0581
4.26-5.220.05413580.9980.0571
5.22-7.380.05610530.9980.0581

-
Processing

Software
NameVersionClassification
PHENIX1.2refinement
XSCALEdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.65→38.52 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 21.72 / Stereochemistry target values: ML
Details: ideal bond length restraints were used for the CYS-RU67 covalent bond
RfactorNum. reflection% reflection
Rfree0.2069 2340 4.83 %
Rwork0.1768 --
obs0.1783 48468 99.92 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.65→38.52 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2837 0 59 297 3193
Refine LS restraintsType: bond length CYS161-RU67 / Dev ideal target: 1.69
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.65-1.680.35171440.33892639X-RAY DIFFRACTION100
1.68-1.720.30421450.28212680X-RAY DIFFRACTION100
1.72-1.760.2711180.23932673X-RAY DIFFRACTION100
1.76-1.80.29041370.22462691X-RAY DIFFRACTION100
1.8-1.850.23331220.22082663X-RAY DIFFRACTION100
1.85-1.910.27051620.23122675X-RAY DIFFRACTION100
1.91-1.970.26261310.20552693X-RAY DIFFRACTION100
1.97-2.040.24021400.1922676X-RAY DIFFRACTION100
2.04-2.120.21871370.17742690X-RAY DIFFRACTION100
2.12-2.220.21661410.17432693X-RAY DIFFRACTION100
2.22-2.330.23841360.17092712X-RAY DIFFRACTION100
2.33-2.480.22881350.18172721X-RAY DIFFRACTION100
2.48-2.670.19191450.17252698X-RAY DIFFRACTION100
2.67-2.940.21881340.17132750X-RAY DIFFRACTION100
2.94-3.370.1931250.17232761X-RAY DIFFRACTION100
3.37-4.240.1771430.15022785X-RAY DIFFRACTION100
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)
12.01931.1860.26022.73892.02263.40510.19920.02080.1189-0.0343-0.28580.1852-0.3223-0.33580.06570.1470.01770.010.2491-0.02670.2254-18.6898-10.92076.0977
20.6164-0.1796-0.222.053-0.65713.97610.0651-0.0235-0.03160.1415-0.0833-0.13350.08660.3132-0.05780.1366-0.0098-0.01060.2101-0.02920.2338-13.8508-17.221118.3507
32.1922-1.2802-0.43772.72250.86012.9253-0.1096-0.16890.18990.5240.1247-0.131-0.00220.3629-0.01650.3515-0.0167-0.03190.22080.00430.211-15.2005-14.136437.6212
43.1728-1.67870.96874.4551-1.76383.2949-0.1081-0.0140.06890.24730.1446-0.5214-0.93120.8242-0.0230.2839-0.15270.08930.3771-0.04850.3609-4.1771-1.92399.2716
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 11 through 77 )
2X-RAY DIFFRACTION2chain 'A' and (resid 78 through 180 )
3X-RAY DIFFRACTION3chain 'A' and (resid 181 through 326 )
4X-RAY DIFFRACTION4chain 'A' and (resid 327 through 358 )

+
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