[English] 日本語
Yorodumi
- PDB-3fyk: Crystal structure of a benzthiophene lead bound to MAPKAP Kinase-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3fyk
TitleCrystal structure of a benzthiophene lead bound to MAPKAP Kinase-2 (MK-2)
ComponentsMAP kinase-activated protein kinase 2
KeywordsTRANSFERASE / MK-2 / MK2 / MAPKAP-2 / Ser/Thr kinase / MAP kinase / Alternative splicing / ATP-binding / Kinase / Nucleotide-binding / Phosphoprotein / Polymorphism / Serine/threonine-protein kinase
Function / homology
Function and homology information


macropinocytosis / CREB phosphorylation / calcium-dependent protein serine/threonine kinase activity / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / leukotriene metabolic process / Synthesis of Leukotrienes (LT) and Eoxins (EX) / regulation of tumor necrosis factor-mediated signaling pathway / regulation of tumor necrosis factor production / calmodulin-dependent protein kinase activity ...macropinocytosis / CREB phosphorylation / calcium-dependent protein serine/threonine kinase activity / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / leukotriene metabolic process / Synthesis of Leukotrienes (LT) and Eoxins (EX) / regulation of tumor necrosis factor-mediated signaling pathway / regulation of tumor necrosis factor production / calmodulin-dependent protein kinase activity / positive regulation of macrophage cytokine production / mitogen-activated protein kinase binding / regulation of interleukin-6 production / 3'-UTR-mediated mRNA stabilization / toll-like receptor signaling pathway / p38MAPK cascade / inner ear development / Regulation of HSF1-mediated heat shock response / cellular response to vascular endothelial growth factor stimulus / vascular endothelial growth factor receptor signaling pathway / regulation of cellular response to heat / p38MAPK events / regulation of mRNA stability / response to cytokine / activated TAK1 mediates p38 MAPK activation / Regulation of TNFR1 signaling / VEGFA-VEGFR2 Pathway / MAPK cascade / positive regulation of tumor necrosis factor production / peptidyl-serine phosphorylation / Oxidative Stress Induced Senescence / response to lipopolysaccharide / calmodulin binding / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / inflammatory response / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA damage response / extracellular exosome / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
MAP kinase activated protein kinase, C-terminal / 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 ...MAP kinase activated protein kinase, C-terminal / 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
Chem-B98 / MAP kinase-activated protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.5 Å
AuthorsKurumbail, R.G. / Caspers, N.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2009
Title: Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency.
Authors: Anderson, D.R. / Meyers, M.J. / Kurumbail, R.G. / Caspers, N. / Poda, G.I. / Long, S.A. / Pierce, B.S. / Mahoney, M.W. / Mourey, R.J. / Parikh, M.D.
History
DepositionJan 22, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 7, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version
Revision 1.3Sep 6, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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
X: MAP kinase-activated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1752
Polymers37,8981
Non-polymers2771
Water0
1
X: MAP kinase-activated protein kinase 2
hetero molecules

X: MAP kinase-activated protein kinase 2
hetero molecules

X: MAP kinase-activated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)114,5256
Polymers113,6933
Non-polymers8323
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation60_665-y+3/2,-z+3/2,x1
crystal symmetry operation78_566z,-x+3/2,-y+3/21
Buried area3720 Å2
ΔGint-23 kcal/mol
Surface area41230 Å2
MethodPISA
2


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)254.598, 254.598, 254.598
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number210
Space group name H-MF4132

-
Components

#1: Protein MAP kinase-activated protein kinase 2 / MAPK-activated protein kinase 2 / MAPKAP kinase 2 / MAPKAPK-2 / MK2


Mass: 37897.750 Da / Num. of mol.: 1 / Fragment: MK-2 kinase module and the auto-inhibitory domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPKAP-2, MAPKAPK2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-DE3
References: UniProt: P49137, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-B98 / (3R)-3-(aminomethyl)-9-methoxy-1,2,3,4-tetrahydro-5H-[1]benzothieno[3,2-e][1,4]diazepin-5-one


Mass: 277.342 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H15N3O2S

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.54 Å3/Da / Density % sol: 72.88 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.4
Details: MK-2 protein at 5 mg/ml equilibrated against a well solution of 1.6 - 2.0 M Sodium malonate at pH 5.4, vapor diffusion, hanging drop, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC / Detector: CCD / Date: Mar 2, 2005
RadiationProtocol: SINGLE WAVELENGTH / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.5→30 Å / Num. obs: 8772 / % possible obs: 93.2 % / Redundancy: 7.5 % / Rmerge(I) obs: 0.083 / Χ2: 0.998 / Net I/σ(I): 19.778
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
3.5-3.626.90.3528600.87795.1
3.62-3.777.20.2718730.88795.3
3.77-3.947.20.2038730.87595
3.94-4.157.40.1668560.87194.4
4.15-4.417.70.1098720.92194.2
4.41-4.757.70.0868810.96493.6
4.75-5.227.80.0788550.97993.1
5.22-5.977.70.0858791.00292.2
5.97-7.57.70.0648931.11491.3
7.5-307.40.0389301.44188.6

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACT3.006data extraction
ADSCQuantumdata collection
HKL-2000data reduction
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1A06,1ATP,1CDK,2PHK

1a06

1atp

1cdk

2phk


Resolution: 3.5→30 Å / Cor.coef. Fo:Fc: 0.895 / Cor.coef. Fo:Fc free: 0.873 / WRfactor Rfree: 0.277 / WRfactor Rwork: 0.24 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.792 / SU B: 27.133 / SU ML: 0.428 / SU Rfree: 0.568 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.568 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.296 424 4.8 %RANDOM
Rwork0.265 ---
obs0.267 8772 93.07 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 146.41 Å2 / Biso mean: 98.046 Å2 / Biso min: 54.67 Å2
Refinement stepCycle: LAST / Resolution: 3.5→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2298 0 19 0 2317
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0222365
X-RAY DIFFRACTIONr_angle_refined_deg1.3971.9733187
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9925279
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.32224.128109
X-RAY DIFFRACTIONr_dihedral_angle_3_deg21.83415451
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.4261516
X-RAY DIFFRACTIONr_chiral_restr0.0780.2347
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0211767
X-RAY DIFFRACTIONr_mcbond_it0.6521.51406
X-RAY DIFFRACTIONr_mcangle_it1.20322283
X-RAY DIFFRACTIONr_scbond_it0.9573959
X-RAY DIFFRACTIONr_scangle_it1.7584.5904
LS refinement shellResolution: 3.498→3.589 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.353 30 -
Rwork0.337 617 -
all-647 -
obs--95.01 %

+
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