[English] 日本語
Yorodumi
- PDB-5nhf: Human Erk2 with an Erk1/2 inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5nhf
TitleHuman Erk2 with an Erk1/2 inhibitor
ComponentsMitogen-activated protein kinase 1
KeywordsTRANSFERASE / Erk2 / kinase / inhibitor / oncology
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 / ERKs are inactivated / cytosine metabolic process ...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 / ERKs are inactivated / cytosine metabolic process / Signaling by MAP2K mutants / Signaling by NODAL / 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 / 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 / positive regulation of telomere maintenance / lung morphogenesis / Recycling pathway of L1 / pseudopodium / Bergmann glial cell differentiation / androgen receptor signaling pathway / Advanced glycosylation endproduct receptor signaling / thyroid gland development / steroid hormone receptor signaling pathway / negative regulation of cell differentiation / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / RHO GTPases Activate WASPs and WAVEs / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Regulation of HSF1-mediated heat shock response / JUN kinase activity / mitogen-activated protein kinase / Signal attenuation / progesterone receptor signaling pathway / Estrogen-stimulated signaling through PRKCZ / phosphatase binding / Schwann cell development / Growth hormone receptor signaling / positive regulation of peptidyl-threonine phosphorylation / 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 / 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 / peptidyl-threonine phosphorylation / 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 / long-term synaptic potentiation / 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
Similarity search - Function
Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. ...Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-8X5 / Mitogen-activated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.14 Å
AuthorsDebreczeni, J.E. / Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Eckersley, K. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. ...Debreczeni, J.E. / Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Eckersley, K. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Hopcroft, P. / Howard, T.D. / Hudson, J. / James, M. / Jones, C.D. / Jones, C.R. / Lamont, S. / Lewis, R. / Lindsay, N. / Roberts, K. / Simpson, I. / StGallay, S. / Swallow, S. / Tonge, M.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Structure-Guided Discovery of Potent and Selective Inhibitors of ERK1/2 from a Modestly Active and Promiscuous Chemical Start Point.
Authors: Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Debreczeni, J.E. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Griffin, N. / Hanson, L. / Hopcroft, P. / ...Authors: Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Debreczeni, J.E. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Griffin, N. / Hanson, L. / Hopcroft, P. / Howard, T.D. / Hudson, J. / James, M. / Jones, C.D. / Jones, C.R. / Lamont, S. / Lewis, R. / Lindsay, N. / Roberts, K. / Simpson, I. / St-Gallay, S. / Swallow, S. / Tang, J. / Tonge, M. / Wang, Z. / Zhai, B.
History
DepositionMar 21, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 19, 2017Provider: repository / Type: Initial release
Revision 1.1May 10, 2017Group: Database references
Revision 1.2Oct 16, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)44,4853
Polymers43,9851
Non-polymers5002
Water1,31573
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area180 Å2
ΔGint-12 kcal/mol
Surface area15330 Å2
MethodPISA
Unit cell
Length a, b, c (Å)49.019, 70.047, 60.363
Angle α, β, γ (deg.)90.00, 109.31, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 43985.414 Da / Num. of mol.: 1
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-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-8X5 / 2-[2-(oxan-4-ylamino)pyrimidin-4-yl]-5-(phenylmethyl)-6,7-dihydro-1~{H}-pyrrolo[3,2-c]pyridin-4-one


Mass: 403.477 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H25N5O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 73 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.22 Å3/Da / Density % sol: 44.68 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop
Details: 30% PegMME2K, 100mM HEPES pH 7.6, 200mM Ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 21, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 2.14→46.26 Å / Num. obs: 20963 / % possible obs: 98.2 % / Redundancy: 3.2 % / Biso Wilson estimate: 46.05 Å2 / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.056 / Net I/av σ(I): 9.5 / Net I/σ(I): 9.5
Reflection shellResolution: 2.14→2.22 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.792 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 1989 / Rpim(I) all: 0.561 / % possible all: 96.4

-
Processing

Software
NameVersionClassification
BUSTER2.11.6refinement
xia2data reduction
Aimlessdata scaling
PHASERphasing
RefinementResolution: 2.14→44.2 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.9 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.281 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.271 / SU Rfree Blow DPI: 0.197 / SU Rfree Cruickshank DPI: 0.202
RfactorNum. reflection% reflectionSelection details
Rfree0.259 1312 6.27 %RANDOM
Rwork0.247 ---
obs0.248 20940 98 %-
Displacement parametersBiso mean: 50.08 Å2
Baniso -1Baniso -2Baniso -3
1-6.4777 Å20 Å21.9325 Å2
2---6.9646 Å20 Å2
3---0.4869 Å2
Refine analyzeLuzzati coordinate error obs: 0.41 Å
Refinement stepCycle: 1 / Resolution: 2.14→44.2 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2649 0 45 73 2767
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012762HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.223766HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d916SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes62HARMONIC2
X-RAY DIFFRACTIONt_gen_planes398HARMONIC5
X-RAY DIFFRACTIONt_it2762HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.19
X-RAY DIFFRACTIONt_other_torsion20.18
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion368SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3424SEMIHARMONIC4
LS refinement shellResolution: 2.14→2.24 Å / Rfactor Rfree error: 0 / Total num. of bins used: 11
RfactorNum. reflection% reflection
Rfree0.393 164 6.11 %
Rwork0.429 2520 -
all0.426 2684 -
obs--95.51 %
Refinement TLS params.Method: refined / Origin x: -4.2987 Å / Origin y: 8.5561 Å / Origin z: 47.5282 Å
111213212223313233
T-0.0442 Å2-0.0206 Å20.0514 Å2-0.019 Å20.0278 Å2--0.0051 Å2
L1.2751 °20.5822 °20.6146 °2-1.1326 °20.5371 °2--1.2335 °2
S-0.1151 Å °0.1186 Å °0.1326 Å °-0.177 Å °0.0889 Å °0.0653 Å °-0.0832 Å °0.04 Å °0.0261 Å °
Refinement TLS groupSelection details: { A|* }

+
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