[English] 日本語
Yorodumi
- PDB-5lar: Crystal structure of p38 alpha MAPK14 in complex with VPC00628 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5lar
TitleCrystal structure of p38 alpha MAPK14 in complex with VPC00628
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / protein kinase / MAPK / inhibitor complex / Structural Genomics / Structural Genomics Consortium / SGC
Function / homology
Function and homology information


p38MAPK events / Activation of the AP-1 family of transcription factors / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / ERK/MAPK targets / myoblast differentiation involved in skeletal muscle regeneration / Regulation of MITF-M-dependent genes involved in pigmentation / activated TAK1 mediates p38 MAPK activation / NOD1/2 Signaling Pathway / Oxidative Stress Induced Senescence ...p38MAPK events / Activation of the AP-1 family of transcription factors / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / ERK/MAPK targets / myoblast differentiation involved in skeletal muscle regeneration / Regulation of MITF-M-dependent genes involved in pigmentation / activated TAK1 mediates p38 MAPK activation / NOD1/2 Signaling Pathway / Oxidative Stress Induced Senescence / ADP signalling through P2Y purinoceptor 1 / Regulation of TP53 Activity through Phosphorylation / Myogenesis / VEGFA-VEGFR2 Pathway / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / positive regulation of myoblast fusion / cartilage condensation / cellular response to UV-B / mitogen-activated protein kinase p38 binding / positive regulation of myotube differentiation / NFAT protein binding / regulation of cytokine production involved in inflammatory response / D-glucose import / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / response to muramyl dipeptide / response to dietary excess / MAP kinase activity / regulation of ossification / cellular response to vascular endothelial growth factor stimulus / JUN kinase activity / mitogen-activated protein kinase / chondrocyte differentiation / negative regulation of hippo signaling / positive regulation of myoblast differentiation / vascular endothelial growth factor receptor signaling pathway / skeletal muscle tissue development / stress-activated MAPK cascade / positive regulation of cardiac muscle cell proliferation / striated muscle cell differentiation / response to muscle stretch / positive regulation of brown fat cell differentiation / positive regulation of interleukin-12 production / Neutrophil degranulation / osteoclast differentiation / lipopolysaccharide-mediated signaling pathway / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / cellular response to ionizing radiation / positive regulation of D-glucose import / stem cell differentiation / response to insulin / placenta development / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / bone development / cellular response to virus / positive regulation of protein import into nucleus / glucose metabolic process / spindle pole / positive regulation of reactive oxygen species metabolic process / osteoblast differentiation / kinase activity / MAPK cascade / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / angiogenesis / response to lipopolysaccharide / transcription by RNA polymerase II / protein kinase activity / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / DNA damage response / positive regulation of gene expression / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / glutamatergic synapse / positive regulation of transcription by RNA polymerase II / mitochondrion / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
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-6SH / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsChaikuad, A. / Petersen, L.K. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Knapp, S. / Structural Genomics Consortium (SGC)
CitationJournal: Medchemcomm / Year: 2016
Title: Novel p38alpha MAP kinase inhibitors identified from yoctoReactor DNA-encoded small molecule library
Authors: Petersen, L.K. / Blakskaer, P. / Chaikuad, A. / Christensen, A.B. / Dietvorst, J. / Holmkvist, J. / Knapp, S. / Korinek, M. / Larsen, L.K. / Pedersen, A.E. / Rohm, S. / Slok, F.A. / Hansen, N.J.V.
History
DepositionJun 14, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 6, 2016Provider: repository / Type: Initial release
Revision 1.1Aug 3, 2016Group: Database references
Revision 1.2Jan 10, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
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 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,8982
Polymers41,3951
Non-polymers5031
Water7,332407
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area17090 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.019, 70.580, 75.029
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 / MAPK 14 / CRK1 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha


Mass: 41395.211 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Mapk14, Crk1, Csbp1, Csbp2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): R3-pRARE2
References: UniProt: P47811, mitogen-activated protein kinase
#2: Chemical ChemComp-6SH / 5-azanyl-~{N}-[[4-[[(2~{S})-1-azanyl-4-cyclohexyl-1-oxidanylidene-butan-2-yl]carbamoyl]phenyl]methyl]-1-phenyl-pyrazole-4-carboxamide


Mass: 502.608 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H34N6O3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 407 / 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: 2.21 Å3/Da / Density % sol: 44.28 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop
Details: 15% medium-molecular weight PEG Smears (MMW PEG smears), 0.1 M MES, pH 6.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.97949 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 8, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97949 Å / Relative weight: 1
ReflectionResolution: 1.5→25.7 Å / Num. obs: 58904 / % possible obs: 99.3 % / Redundancy: 5.8 % / Rmerge(I) obs: 0.102 / Net I/σ(I): 9.7
Reflection shellResolution: 1.5→1.58 Å / Redundancy: 4.7 % / Rmerge(I) obs: 0.428 / Mean I/σ(I) obs: 3.1 / % possible all: 96.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0073refinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4LOO

4loo


Resolution: 1.5→25.7 Å / Cor.coef. Fo:Fc: 0.968 / Cor.coef. Fo:Fc free: 0.955 / SU B: 2.709 / SU ML: 0.052 / Cross valid method: THROUGHOUT / ESU R: 0.072 / ESU R Free: 0.076 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.20504 2774 4.7 %RANDOM
Rwork0.16913 ---
obs0.17086 56060 99.17 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 24.966 Å2
Baniso -1Baniso -2Baniso -3
1-0.91 Å20 Å20 Å2
2---0.28 Å20 Å2
3----0.64 Å2
Refinement stepCycle: 1 / Resolution: 1.5→25.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2811 0 37 407 3255
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0192967
X-RAY DIFFRACTIONr_bond_other_d0.0010.022844
X-RAY DIFFRACTIONr_angle_refined_deg1.5511.9554037
X-RAY DIFFRACTIONr_angle_other_deg0.81136545
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4415363
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.43123.768138
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.6215513
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.9231520
X-RAY DIFFRACTIONr_chiral_restr0.1030.2447
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0213440
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02694
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it4.9033.0421416
X-RAY DIFFRACTIONr_mcbond_other4.9013.0421417
X-RAY DIFFRACTIONr_mcangle_it6.425.6631774
X-RAY DIFFRACTIONr_mcangle_other6.425.671774
X-RAY DIFFRACTIONr_scbond_it7.0423.761551
X-RAY DIFFRACTIONr_scbond_other7.043.7611552
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other8.6796.612258
X-RAY DIFFRACTIONr_long_range_B_refined9.69819.5653786
X-RAY DIFFRACTIONr_long_range_B_other9.719.5463782
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.5→1.539 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.299 161 -
Rwork0.236 3861 -
obs--93.23 %
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)
10.5359-0.45950.14650.8135-0.71161.28360.09970.01040.1144-0.0439-0.1309-0.1734-0.05830.16410.03120.0298-0.01120.030.07380.00730.087565.09265.58217.951
20.3358-0.2992-0.09520.42390.15620.4364-0.0323-0.00710.0290.05280.0226-0.0437-0.004-0.00030.00970.0445-0.0041-0.00660.04890.00840.047337.43969.2121.509
30.3857-0.07710.15790.4499-0.02620.49130.0454-0.0237-0.0785-0.0297-0.00970.05180.0379-0.0599-0.03560.015-0.0102-0.00490.04060.01390.031339.39660.80118.844
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A4 - 106
2X-RAY DIFFRACTION2A107 - 258
3X-RAY DIFFRACTION3A259 - 353

+
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