[English] 日本語
Yorodumi
- PDB-5v62: Phospho-ERK2 bound to bivalent inhibitor SBP3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5v62
TitlePhospho-ERK2 bound to bivalent inhibitor SBP3
Components
  • Mitogen-activated protein kinase 1
  • Ribosomal protein S6 kinase alpha-1
KeywordsTRANSFERASE/INHIBITOR / kinase / MAPK / phosphorylation / cancer / TRANSFERASE / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


regulation of translation in response to stress / CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling / ribosomal protein S6 kinase activity / CREB phosphorylation / hepatocyte proliferation / positive regulation of hepatic stellate cell activation / phospho-PLA2 pathway / Signaling by MAPK mutants / RAF-independent MAPK1/3 activation / Suppression of apoptosis ...regulation of translation in response to stress / CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling / ribosomal protein S6 kinase activity / CREB phosphorylation / hepatocyte proliferation / positive regulation of hepatic stellate cell activation / 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 / negative regulation of TOR signaling / 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 / regulation of cytoskeleton organization / Activation of the AP-1 family of transcription factors / face development / ERK/MAPK targets / androgen receptor signaling pathway / RUNX2 regulates osteoblast differentiation / pseudopodium / : / positive regulation of telomere capping / Recycling pathway of L1 / MAPK1 (ERK2) activation / Bergmann glial cell differentiation / thyroid gland development / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / negative regulation of cell differentiation / Advanced glycosylation endproduct receptor signaling / steroid hormone receptor signaling pathway / MAP kinase activity / RHO GTPases Activate NADPH Oxidases / Regulation of HSF1-mediated heat shock response / regulation of ossification / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / RHO GTPases Activate WASPs and WAVEs / mitogen-activated protein kinase / 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 / stress-activated MAPK cascade / lipopolysaccharide-mediated signaling pathway / positive regulation of telomere maintenance via telomerase / protein serine/threonine/tyrosine kinase activity / NPAS4 regulates expression of target genes / cellular response to cadmium ion / myelination / ERK1 and ERK2 cascade / cellular response to amino acid starvation / phosphotyrosine residue binding / 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 / positive regulation of cell differentiation / FCERI mediated MAPK activation / long-term synaptic potentiation / response to nicotine / Negative regulation of FGFR3 signaling / FCGR3A-mediated phagocytosis / peptidyl-threonine phosphorylation / B cell receptor signaling pathway
Similarity search - Function
Ribosomal S6 kinase, N-terminal catalytic domain / Ribosomal protein S6 kinase II / Mitogen-activated protein (MAP) kinase, ERK1/2 / Protein kinase, C-terminal / Protein kinase C terminal domain / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal ...Ribosomal S6 kinase, N-terminal catalytic domain / Ribosomal protein S6 kinase II / Mitogen-activated protein (MAP) kinase, ERK1/2 / Protein kinase, C-terminal / Protein kinase C terminal domain / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / 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-(hex-5-yn-1-yl)hexanamide / Chem-FRZ / Mitogen-activated protein kinase 1 / Ribosomal protein S6 kinase alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / molecular replacement / Resolution: 1.9 Å
AuthorsLechtenberg, B.C. / Riedl, S.J.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA160457 United States
CitationJournal: ACS Med Chem Lett / Year: 2017
Title: Structure-Guided Strategy for the Development of Potent Bivalent ERK Inhibitors.
Authors: Lechtenberg, B.C. / Mace, P.D. / Sessions, E.H. / Williamson, R. / Stalder, R. / Wallez, Y. / Roth, G.P. / Riedl, S.J. / Pasquale, E.B.
History
DepositionMar 15, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 26, 2017Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Apr 18, 2018Group: Advisory / Data collection / Database references / Category: citation / pdbx_unobs_or_zero_occ_atoms
Item: _citation.journal_abbrev / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.3Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Jul 10, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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
I: Ribosomal protein S6 kinase alpha-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,2999
Polymers43,3162
Non-polymers9837
Water4,594255
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3130 Å2
ΔGint-8 kcal/mol
Surface area17360 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.327, 77.888, 152.938
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AI

#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: 40918.828 Da / Num. of mol.: 1 / Fragment: UNP residues 10-360
Source method: isolated from a genetically manipulated source
Details: Dual phosphorylated ERK2 / 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: Protein/peptide Ribosomal protein S6 kinase alpha-1 / S6K-alpha-1 / 90 kDa ribosomal protein S6 kinase 1 / p90S6K / MAP kinase-activated protein kinase ...S6K-alpha-1 / 90 kDa ribosomal protein S6 kinase 1 / p90S6K / MAP kinase-activated protein kinase 1a / MAPKAPK-1a / Ribosomal S6 kinase 1 / RSK-1


Mass: 2396.858 Da / Num. of mol.: 1 / Fragment: UNP residues 713-729 / Source method: obtained synthetically / Details: Bivalent ERK inhibitor / Source: (synth.) Homo sapiens (human)
References: UniProt: Q15418, non-specific serine/threonine protein kinase

-
Non-polymers , 4 types, 262 molecules

#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-FRZ / 5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINE / FR180204


Mass: 327.343 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H13N7
#5: Chemical ChemComp-AKS / N-(hex-5-yn-1-yl)hexanamide


Mass: 195.301 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H21NO
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 255 / Source method: isolated from a natural source / Formula: H2O

-
Details

Nonpolymer detailsLigand AKS links FRZ and azido-lysine (AZK) of peptide inhibitor to form bivalent ERK inhibitor SBP3

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.92 Å3/Da / Density % sol: 57.88 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 0.1 M Tris-Bicine pH 8.5, 0.02 M each of 1,6-Hexanediol, 1-Butanol, 1,2-Propanediol, 2-Propanol, 1,4-Butanediol, 1,3-Propanediol, 20% v/v PEG550MME, 10% w/v PEG20,000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.97852 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 11, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97852 Å / Relative weight: 1
ReflectionResolution: 1.9→19.79 Å / Num. obs: 40711 / % possible obs: 99.8 % / Redundancy: 6.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.051 / Rpim(I) all: 0.022 / Rrim(I) all: 0.056 / Net I/σ(I): 21.4 / Num. measured all: 266416 / Scaling rejects: 0
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsCC1/2Rpim(I) allRrim(I) all% possible all
1.9-1.946.81.1120.6650.4581.20499.8
8.91-19.795.60.01710.0080.01990.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMACrefinement
Aimless0.3.8data scaling
PDB_EXTRACT3.22data extraction
XDSdata reduction
PHASERphasing
Cootmodel building
RefinementResolution: 1.9→19.79 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.954 / WRfactor Rfree: 0.1908 / WRfactor Rwork: 0.1623 / FOM work R set: 0.8565 / SU B: 6.338 / SU ML: 0.09 / SU R Cruickshank DPI: 0.1222 / SU Rfree: 0.1169 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.122 / ESU R Free: 0.117 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2033 2030 5 %RANDOM
Rwork0.1709 ---
obs0.1725 38622 99.63 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK
Displacement parametersBiso max: 107.89 Å2 / Biso mean: 41.355 Å2 / Biso min: 22.79 Å2
Baniso -1Baniso -2Baniso -3
1--0.75 Å20 Å20 Å2
2--0.8 Å20 Å2
3----0.06 Å2
Refinement stepCycle: final / Resolution: 1.9→19.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2990 0 30 255 3275
Biso mean--78.3 47.21 -
Num. residues----367
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0193236
X-RAY DIFFRACTIONr_bond_other_d0.0020.023013
X-RAY DIFFRACTIONr_angle_refined_deg1.6981.9984390
X-RAY DIFFRACTIONr_angle_other_deg0.98137013
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0635388
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.74723.907151
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.01415572
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.4621522
X-RAY DIFFRACTIONr_chiral_restr0.0930.2474
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0213541
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02655
LS refinement shellResolution: 1.9→1.949 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.306 131 -
Rwork0.275 2792 -
all-2923 -
obs--99.73 %
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)
10.86340.2242-0.01390.96060.26921.75570.0396-0.0236-0.04640.19080.0302-0.03830.12950.083-0.06980.05010.0278-0.01030.0438-0.00270.00565.981618.45323.7987
24.2666-0.8045-1.85339.59452.05521.8570.09960.23580.7544-0.2720.2364-0.1917-0.5401-0.021-0.3360.286-0.00250.01670.11270.03230.13447.333436.310714.4722
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A10 - 360
2X-RAY DIFFRACTION2I713 - 726

+
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