[English] 日本語
Yorodumi
- PDB-3fkl: P38 kinase crystal structure in complex with RO9552 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3fkl
TitleP38 kinase crystal structure in complex with RO9552
ComponentsMitogen-activated protein kinase 14
KeywordsSIGNALING PROTEIN / TRANSFERASE / P38 / MAP KINASE / SERINE/THREONINE KINASE / ATP-binding / Kinase / Nucleotide-binding / Nucleus / Phosphoprotein / Serine/threonine-protein kinase
Function / homology
Function and homology information


stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / CD163 mediating an anti-inflammatory response / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of myoblast fusion ...stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / CD163 mediating an anti-inflammatory response / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of myoblast fusion / cellular response to UV-B / cartilage condensation / mitogen-activated protein kinase p38 binding / positive regulation of muscle cell differentiation / Platelet sensitization by LDL / Myogenesis / NFAT protein binding / positive regulation of myotube differentiation / regulation of cytokine production involved in inflammatory response / Activation of the AP-1 family of transcription factors / D-glucose import / p38MAPK cascade / ERK/MAPK targets / response to dietary excess / fatty acid oxidation / cellular response to lipoteichoic acid / response to muramyl dipeptide / Regulation of MITF-M-dependent genes involved in pigmentation / MAP kinase kinase activity / signal transduction in response to DNA damage / regulation of ossification / MAP kinase activity / cellular response to vascular endothelial growth factor stimulus / RHO GTPases Activate NADPH Oxidases / mitogen-activated protein kinase / chondrocyte differentiation / negative regulation of hippo signaling / vascular endothelial growth factor receptor signaling pathway / positive regulation of myoblast differentiation / stress-activated MAPK cascade / skeletal muscle tissue development / positive regulation of cardiac muscle cell proliferation / p38MAPK events / positive regulation of brown fat cell differentiation / striated muscle cell differentiation / response to muscle stretch / positive regulation of interleukin-12 production / osteoclast differentiation / positive regulation of erythrocyte differentiation / lipopolysaccharide-mediated signaling pathway / DNA damage checkpoint signaling / placenta development / tumor necrosis factor-mediated signaling pathway / cellular response to ionizing radiation / positive regulation of D-glucose import / activated TAK1 mediates p38 MAPK activation / stem cell differentiation / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt signaling pathway / NOD1/2 Signaling Pathway / response to insulin / bone development / cellular response to virus / platelet activation / positive regulation of protein import into nucleus / VEGFA-VEGFR2 Pathway / glucose metabolic process / cell morphogenesis / positive regulation of reactive oxygen species metabolic process / chemotaxis / spindle pole / osteoblast differentiation / ADP signalling through P2Y purinoceptor 1 / cellular senescence / MAPK cascade / cellular response to lipopolysaccharide / angiogenesis / secretory granule lumen / protein phosphatase binding / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / ficolin-1-rich granule lumen / transcription by RNA polymerase II / cell surface receptor signaling pathway / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / glutamatergic synapse / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding
Similarity search - Function
Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / 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 / Protein kinase domain ...Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / 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 / 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-FKL / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2 Å
AuthorsKuglstatter, A. / Ghate, M.
CitationJournal: To be Published
Title: Mapping Binding Pocket Volume: Potential Applications towards Ligand Design and Selectivity
Authors: Arora, N. / Williams, C. / Delano, W. / Will, D. / Kuglstatter, A.
History
DepositionDec 17, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 22, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Refinement description / Version format compliance
Revision 1.2Jul 24, 2019Group: Data collection / Refinement description / Category: software
Item: _software.classification / _software.name / _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_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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
A: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,1822
Polymers42,7491
Non-polymers4341
Water2,936163
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)46.035, 86.233, 125.508
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 14 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha / Cytokine suppressive anti- ...Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha / Cytokine suppressive anti-inflammatory drug-binding protein / CSAID-binding protein / CSBP / MAX-interacting protein 2 / MAP kinase MXI2 / SAPK2A


Mass: 42748.715 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CSBP, CSBP1, CSBP2, CSPB1, MAPK14, MXI2 / Production host: Escherichia coli (E. coli)
References: UniProt: Q16539, mitogen-activated protein kinase
#2: Chemical ChemComp-FKL / N-cyclopropyl-4-methyl-3-[8-methyl-7-oxo-2-(tetrahydro-2H-pyran-4-ylamino)-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl]benzamide


Mass: 433.503 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H27N5O3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 163 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.91 Å3/Da / Density % sol: 57.79 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 7.6
Details: 50 mM Hepes pH 7.6, 50 mM CaCl2, 17% PEG 3350, VAPOR DIFFUSION, HANGING DROP, temperature 290K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1
DetectorType: ADSC QUANTUM 210 / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2→50 Å / Num. obs: 32876 / % possible obs: 95.6 % / Biso Wilson estimate: 37.1 Å2 / Rsym value: 0.065
Reflection shellResolution: 2→2.07 Å / Mean I/σ(I) obs: 1.9 / Num. unique all: 3096 / Rsym value: 0.595 / % possible all: 92.3

-
Processing

Software
NameVersionClassification
REFMAC5.2.0005refinement
CNSrefinement
ADSCQuantumdata collection
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB entry 1P38

1p38
PDB Unreleased entry


Resolution: 2→34.1 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.929 / SU B: 9.442 / SU ML: 0.118 / TLS residual ADP flag: LIKELY RESIDUAL / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / ESU R: 0.178 / ESU R Free: 0.162 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.25391 1655 5 %RANDOM
Rwork0.21876 ---
obs0.22051 31168 95.36 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 39.686 Å2
Baniso -1Baniso -2Baniso -3
1--0.79 Å20 Å20 Å2
2---0.09 Å20 Å2
3---0.88 Å2
Refinement stepCycle: LAST / Resolution: 2→34.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2773 0 32 163 2968
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0222875
X-RAY DIFFRACTIONr_angle_refined_deg1.0021.983907
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.0035342
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.6223.985133
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.46315495
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.331518
X-RAY DIFFRACTIONr_chiral_restr0.0680.2435
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.022173
X-RAY DIFFRACTIONr_nbd_refined0.1920.21263
X-RAY DIFFRACTIONr_nbtor_refined0.3030.21990
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1230.2170
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1440.223
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.120.213
X-RAY DIFFRACTIONr_mcbond_it0.6171.51785
X-RAY DIFFRACTIONr_mcangle_it1.06722793
X-RAY DIFFRACTIONr_scbond_it1.19931283
X-RAY DIFFRACTIONr_scangle_it1.9264.51111
LS refinement shellResolution: 2→2.055 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.391 110 -
Rwork0.286 2091 -
obs--88.82 %
Refinement TLS params.Method: refined / Origin x: 21.1936 Å / Origin y: 16.5771 Å / Origin z: 21.5093 Å
111213212223313233
T-0.0312 Å20.007 Å2-0.0107 Å2--0.0166 Å20.0155 Å2---0.0155 Å2
L0.2854 °20.1792 °2-0.2587 °2-0.6479 °2-0.127 °2--0.4067 °2
S-0.006 Å °0.014 Å °-0.0303 Å °-0.0315 Å °0.0476 Å °0.0721 Å °0.019 Å °0.0192 Å °-0.0416 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1001 - 2154
2X-RAY DIFFRACTION1A361
3X-RAY DIFFRACTION1A4 - 352

+
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