[English] 日本語
Yorodumi
- PDB-8r5f: ERK2 covalently bound to RU83 cyclohexenone based inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8r5f
TitleERK2 covalently bound to RU83 cyclohexenone based inhibitor
ComponentsMitogen-activated protein kinase 1
KeywordsSIGNALING PROTEIN / MAPK / MAP kinase / Kinase / Inhibitor / Covalent Inhibitor / ERK2 / Mitogen-activated protein kinase 1
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 / Signaling by MAP2K mutants ...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 / Signaling by MAP2K mutants / Signaling by NODAL / ERKs are inactivated / response to epidermal growth factor / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / Regulation of the apoptosome activity / positive regulation of macrophage proliferation / regulation of cellular pH / outer ear morphogenesis / Signaling by LTK in cancer / regulation of Golgi inheritance / labyrinthine layer blood vessel development / ERBB signaling pathway / 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 / 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 / Recycling pathway of L1 / pseudopodium / Bergmann glial cell differentiation / androgen receptor signaling pathway / thyroid gland development / steroid hormone receptor signaling pathway / Advanced glycosylation endproduct receptor signaling / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / negative regulation of cell differentiation / 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 / JUN kinase activity / mitogen-activated protein kinase / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / phosphatase binding / Schwann cell development / Growth hormone receptor signaling / progesterone receptor signaling pathway / stress-activated MAPK cascade / Nuclear events stimulated by ALK signaling in cancer / NPAS4 regulates expression of target genes / phosphotyrosine residue binding / myelination / RNA polymerase II CTD heptapeptide repeat kinase activity / peptidyl-threonine phosphorylation / Transcriptional and post-translational regulation of MITF-M expression and activity / NCAM signaling for neurite out-growth / ERK1 and ERK2 cascade / cellular response to amino acid starvation / insulin-like growth factor receptor signaling pathway / lipopolysaccharide-mediated signaling pathway / ESR-mediated signaling / thymus development / Regulation of PTEN gene transcription / Signal transduction by L1 / B cell receptor signaling pathway / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / response to nicotine / Negative regulation of FGFR3 signaling / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Negative regulation of FGFR1 signaling / positive regulation of cholesterol biosynthetic process / 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 / long-term synaptic potentiation
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.
Funding support Hungary, 1items
OrganizationGrant numberCountry
Hungarian National Research, Development and Innovation OfficeKKP 126963 Hungary
CitationJournal: To Be Published
Title: The covalent coordination of cyclohexenone inhibitors in the MAP kinase docking groove
Authors: Poti, A. / Sok, P. / Remenyi, A.
History
DepositionNov 16, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 27, 2024Provider: repository / Type: Initial release

-
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)42,6404
Polymers41,7471
Non-polymers8933
Water2,126118
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1180 Å2
ΔGint-3 kcal/mol
Surface area15640 Å2
Unit cell
Length a, b, c (Å)41.486, 77.081, 123.251
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 RU83 covalent inhibitor in 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-Y3H / ~{O}3-~{tert}-butyl ~{O}1-prop-2-ynyl (1~{S},3~{S})-1-methyl-4-oxidanylidene-cyclohexane-1,3-dicarboxylate


Mass: 294.343 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H22O5 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 118 / 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: 2.43 Å3/Da / Density % sol: 49.5 % / Description: rhomboid
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 10% PEG 8000, 0.1 M TRIS pH 8.5, 1.25 M NaCl as reservoir

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P14 (MX2) / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 15, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.65→123.25 Å / Num. obs: 48540 / % possible obs: 100 % / Redundancy: 13.4 % / CC1/2: 0.999 / Rmerge(I) obs: 0.059 / Rpim(I) all: 0.017 / Rrim(I) all: 0.061 / Χ2: 1.01 / Net I/σ(I): 19.6 / Num. measured all: 651533
Reflection shellResolution: 1.65→1.68 Å / % possible obs: 100 % / Redundancy: 13.8 % / Rmerge(I) obs: 1.895 / Num. measured all: 32888 / Num. unique obs: 2376 / CC1/2: 0.678 / Rpim(I) all: 0.528 / Rrim(I) all: 1.968 / Χ2: 1.06 / Net I/σ(I) obs: 1.5

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.65→65.35 Å / SU ML: 0.2 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.07 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2178 1998 4.12 %
Rwork0.193 --
obs0.194 48456 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.65→65.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2725 0 58 118 2901
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.014
X-RAY DIFFRACTIONf_angle_d1.403
X-RAY DIFFRACTIONf_dihedral_angle_d14.3451111
X-RAY DIFFRACTIONf_chiral_restr0.085436
X-RAY DIFFRACTIONf_plane_restr0.012504
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.65-1.690.34971400.35013248X-RAY DIFFRACTION100
1.69-1.740.24261420.27353296X-RAY DIFFRACTION100
1.74-1.790.25111390.23463254X-RAY DIFFRACTION100
1.79-1.850.26781400.22923257X-RAY DIFFRACTION100
1.85-1.910.27931410.2283292X-RAY DIFFRACTION100
1.91-1.990.25521420.22463301X-RAY DIFFRACTION100
1.99-2.080.19691420.19333286X-RAY DIFFRACTION100
2.08-2.190.24651420.1873297X-RAY DIFFRACTION100
2.19-2.330.20391410.18953299X-RAY DIFFRACTION100
2.33-2.510.24461430.2013302X-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)
16.9808-0.0718-5.05767.75644.48288.04360.3916-0.14580.4192-0.1085-0.53170.69-0.5409-0.44010.14020.22940.043-0.04880.4173-0.07680.2867-24.8193-12.61421.2163
23.61782.47910.33116.05694.55536.52180.24360.05680.12360.1283-0.56710.4756-0.2387-0.62190.330.18390.0273-0.03310.3078-0.01370.2058-19.1507-12.33465.2782
30.8954-0.2742-0.59466.5145-1.30857.03350.1119-0.05110.0684-0.02120.0578-0.0976-0.42710.3596-0.1240.1308-0.04950.03250.2993-0.04680.2768-10.0382-8.42179.4232
41.0536-0.22650.43031.9072-0.166.24460.1092-0.1082-0.16570.28010.01-0.040.79310.0496-0.11570.3362-0.0165-0.040.2251-0.02170.2657-16.8836-22.328121.4201
59.09693.87982.73792.35632.61657.2593-0.04620.14770.81370.40740.1203-0.0433-0.42110.7258-0.07160.3781-0.0521-0.01670.3069-0.02010.3591-10.1039-10.737122.5149
68.49920.4970.99293.13891.7248.32560.03950.18920.54940.27840.192-0.0676-0.27040.3701-0.21880.3799-0.0407-0.01930.21190.02220.1988-15.5374-12.042933.353
76.39950.03754.38667.79545.62539.2774-0.1257-0.25810.35760.0548-0.0880.1699-0.3547-0.23160.21080.4502-0.01410.04260.2866-0.00850.2816-24.5746-9.71238.3881
84.748-1.78131.11741.0226-1.75488.24010.0198-0.08890.3135-0.27490.0231-0.92950.22830.7398-0.08390.6225-0.0438-0.06730.3873-0.12440.505-11.7267-2.702647.521
92.0358-0.6707-0.83362.40510.49944.02070.0264-0.3621-0.18960.57460.109-0.11130.93390.7213-0.09920.65560.0965-0.12110.39430.00920.2973-12.8143-23.398138.0369
104.2401-1.84020.53187.2971-1.63674.56740.0092-0.20580.15160.16170.1273-0.7737-0.97670.8988-0.170.2899-0.14970.10420.4372-0.06730.4324-3.7555-2.22459.423
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 11 through 33 )
2X-RAY DIFFRACTION2chain 'A' and (resid 34 through 61 )
3X-RAY DIFFRACTION3chain 'A' and (resid 62 through 100 )
4X-RAY DIFFRACTION4chain 'A' and (resid 101 through 162 )
5X-RAY DIFFRACTION5chain 'A' and (resid 163 through 190 )
6X-RAY DIFFRACTION6chain 'A' and (resid 191 through 223 )
7X-RAY DIFFRACTION7chain 'A' and (resid 224 through 244 )
8X-RAY DIFFRACTION8chain 'A' and (resid 245 through 266 )
9X-RAY DIFFRACTION9chain 'A' and (resid 267 through 326 )
10X-RAY DIFFRACTION10chain '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