[English] 日本語
Yorodumi
- PDB-1ove: The structure of p38 alpha in complex with a dihydroquinolinone -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1ove
TitleThe structure of p38 alpha in complex with a dihydroquinolinone
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / MAp kinase / hydrophobic pocket / kinase domain / linker region
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 / CD163 mediating an anti-inflammatory response / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / positive regulation of myoblast fusion / KSRP (KHSRP) binds and destabilizes mRNA ...stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / CD163 mediating an anti-inflammatory response / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / positive regulation of myoblast fusion / KSRP (KHSRP) binds and destabilizes mRNA / cartilage condensation / cellular response to UV-B / positive regulation of muscle cell differentiation / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / Myogenesis / positive regulation of myotube differentiation / NFAT protein binding / regulation of cytokine production involved in inflammatory response / D-glucose import / Activation of the AP-1 family of transcription factors / p38MAPK cascade / ERK/MAPK targets / Regulation of MITF-M-dependent genes involved in pigmentation / fatty acid oxidation / MAP kinase kinase activity / cellular response to lipoteichoic acid / response to muramyl dipeptide / response to dietary excess / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / cellular response to vascular endothelial growth factor stimulus / signal transduction in response to DNA damage / 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 / p38MAPK events / striated muscle cell differentiation / response to muscle stretch / positive regulation of brown fat cell differentiation / positive regulation of interleukin-12 production / 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 / activated TAK1 mediates p38 MAPK activation / stem cell differentiation / response to insulin / placenta development / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt signaling pathway / NOD1/2 Signaling Pathway / cell morphogenesis / bone development / cellular response to virus / platelet activation / VEGFA-VEGFR2 Pathway / positive regulation of protein import into nucleus / glucose metabolic process / spindle pole / chemotaxis / positive regulation of reactive oxygen species metabolic process / osteoblast differentiation / cellular senescence / ADP signalling through P2Y purinoceptor 1 / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / secretory granule lumen / Oxidative Stress Induced Senescence / angiogenesis / 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
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-358 / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.1 Å
AuthorsFitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G.
Citation
Journal: Nat.Struct.Biol. / Year: 2003
Title: Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity
Authors: Fitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G.
#1: Journal: Bioorg.Med.Chem.Lett. / Year: 2003
Title: Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase
Authors: Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E. / Wang, Z. / Cameron, P.M. / Nichols, E.A. / O'Keefe, S.J. / O'Neill, E.A. / Schmatz, D.M. / ...Authors: Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E. / Wang, Z. / Cameron, P.M. / Nichols, E.A. / O'Keefe, S.J. / O'Neill, E.A. / Schmatz, D.M. / Schwartz, C.D. / Thompson, C.M. / Zaller, D.M. / Doherty, J.B.
History
DepositionMar 26, 2003Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 2, 2003Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Non-polymer description / Version format compliance
Revision 1.3Oct 27, 2021Group: Database references / Derived calculations / Category: database_2 / 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
Revision 1.4Aug 16, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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)42,5623
Polymers41,9831
Non-polymers5792
Water5,188288
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)45.009, 87.100, 122.613
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 / MAP kinase p38 / Cytokine suppressive anti-inflammatory drug ...Mitogen-activated protein kinase p38 / MAP kinase p38 / Cytokine suppressive anti-inflammatory drug binding protein / CSAID binding protein / CSBP / MAX-interacting protein 2 / MAP kinase MXI2


Mass: 41982.871 Da / Num. of mol.: 1 / Mutation: C162S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14 / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q16539, EC: 2.7.1.37
#2: Chemical ChemComp-358 / 1-(2,6-DICHLOROPHENYL)-5-(2,4-DIFLUOROPHENYL)-7-PIPERIDIN-4-YL-3,4-DIHYDROQUINOLIN-2(1H)-ONE


Mass: 487.368 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H22Cl2F2N2O
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 288 / 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: 2.71 Å3/Da / Density % sol: 54.22 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7
Details: Sodium citrate, Ammonium sulfate, HEPES buffer, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Crystal grow
*PLUS
pH: 7.5 / Method: vapor diffusion / Details: Wilson, K.P., (1996) J.Biol.Chem., 271, 27696.
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDChemical formula
124 mg/mlprotein1drop
230 mMHEPES1drop
36 mMDTT1drop
40.06 M1dropNaCl
53 %glycerol1drop
616 mMNa HEPES1drop
70.224 Msodium citrate1drop
852 mMammonium sulfate1drop
940 mMNa HEPES1reservoir
100.56 Msodium citrate1reservoir
11130 mMammonium sulfate1reservoir

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Dec 15, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→35 Å / Num. all: 29093 / Num. obs: 29079 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 7.1 % / Biso Wilson estimate: 25.3 Å2 / Rsym value: 0.094 / Net I/σ(I): 6.2
Reflection shellResolution: 2.1→2.18 Å / Redundancy: 6.6 % / Mean I/σ(I) obs: 1.7 / Num. unique all: 2867 / Rsym value: 0.399 / % possible all: 100
Reflection
*PLUS
% possible obs: 100 % / Rmerge(I) obs: 0.094
Reflection shell
*PLUS
% possible obs: 100 % / Num. unique obs: 2867 / Rmerge(I) obs: 0.399

-
Processing

Software
NameClassification
HKL-2000data collection
SCALEPACKdata scaling
CNSrefinement
HKL-2000data reduction
CNSphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1OUK

1ouk


Resolution: 2.1→25 Å / Isotropic thermal model: Anisotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber / Details: As implemented in CNX
RfactorNum. reflection% reflectionSelection details
Rfree0.233 1426 5 %Random; 5% data flagged
Rwork0.192 ---
obs0.195 28922 100 %-
all-28930 --
Solvent computationSolvent model: MASK / Bsol: 0.39 Å2 / ksol: 48.66 e/Å3
Displacement parametersBiso mean: 29 Å2
Baniso -1Baniso -2Baniso -3
1-7.485 Å22.979 Å2-10.464 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.29 Å0.23 Å
Luzzati d res low-5 Å
Luzzati sigma a0.23 Å0.16 Å
Refinement stepCycle: LAST / Resolution: 2.1→25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2807 0 39 288 3134
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.011
X-RAY DIFFRACTIONc_angle_deg1.42
X-RAY DIFFRACTIONc_dihedral_angle_d22.1
X-RAY DIFFRACTIONc_improper_angle_d0.89
LS refinement shellResolution: 2.1→2.18 Å
RfactorNum. reflection% reflection
Rfree0.302 122 5 %
Rwork0.228 2731 -
obs-2853 100 %
Refinement
*PLUS
Lowest resolution: 25 Å
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_dihedral_angle_d
X-RAY DIFFRACTIONc_dihedral_angle_deg22.1
X-RAY DIFFRACTIONc_improper_angle_d
X-RAY DIFFRACTIONc_improper_angle_deg0.89

+
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