[English] 日本語
Yorodumi
- PDB-9d7n: Human p38alpha MAP Kinase in complex with 1-Isobutyl-1H-indazole ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9d7n
TitleHuman p38alpha MAP Kinase in complex with 1-Isobutyl-1H-indazole derivative; OSF267
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / P38 / KINASE / INHIBITOR / COMPLEX
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 / CD163 mediating an anti-inflammatory response / cell surface receptor protein serine/threonine kinase signaling pathway / 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 / CD163 mediating an anti-inflammatory response / cell surface receptor protein serine/threonine kinase signaling pathway / 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 / Regulation of MITF-M-dependent genes involved in pigmentation / response to dietary excess / fatty acid oxidation / cellular response to lipoteichoic acid / response to muramyl dipeptide / 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 / negative regulation of hippo signaling / chondrocyte differentiation / positive regulation of myoblast differentiation / vascular endothelial growth factor receptor signaling pathway / 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 / cellular response to ionizing radiation / activated TAK1 mediates p38 MAPK activation / osteoclast differentiation / lipopolysaccharide-mediated signaling pathway / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / placenta development / tumor necrosis factor-mediated signaling pathway / positive regulation of D-glucose import / NOD1/2 Signaling Pathway / stem cell differentiation / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt 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 / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / angiogenesis / protein phosphatase binding / secretory granule lumen / 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. / : / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. ...Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase 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
Similarity search - Domain/homology
: / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.973 Å
AuthorsBrunzelle, J.S. / Shuvalova, L. / Benetik, S.F. / Roy, S.M. / Watterson, D.M. / Gobec, S.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: J.Med.Chem. / Year: 2025
Title: Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38 alpha Mitogen-Activated Protein Kinase Inhibitors.
Authors: Ferjancic Benetik, S. / Proj, M. / Knez, D. / Kosak, U. / Meden, A. / Krajsek, K. / Pislar, A. / Horvat, S. / Svajger, U. / Tesic, N. / Pulkrabkova, L. / Soukup, O. / Skarka, A. / Andrys, R. ...Authors: Ferjancic Benetik, S. / Proj, M. / Knez, D. / Kosak, U. / Meden, A. / Krajsek, K. / Pislar, A. / Horvat, S. / Svajger, U. / Tesic, N. / Pulkrabkova, L. / Soukup, O. / Skarka, A. / Andrys, R. / Brazzolotto, X. / Igert, A. / Nachon, F. / Dias, J. / Detka, J. / Gdula-Argasinska, J. / Wyska, E. / Szafarz, M. / Manik, A. / Plachtij, N. / Musilek, K. / Salat, K. / Obreza, A. / Gobec, S.
History
DepositionAug 16, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 24, 2025Provider: repository / Type: Initial release

-
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)40,4383
Polymers39,7851
Non-polymers6542
Water1,45981
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)66.392, 75.381, 79.241
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Mitogen-activated protein kinase 14 / MAP kinase 14 / MAPK 14 / Cytokine suppressive anti-inflammatory drug-binding protein / CSAID- ...MAP kinase 14 / MAPK 14 / Cytokine suppressive anti-inflammatory drug-binding protein / CSAID-binding protein / CSBP / MAP kinase MXI2 / MAX-interacting protein 2 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha / Stress-activated protein kinase 2a / SAPK2a


Mass: 39784.582 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A / Production host: Escherichia coli (E. coli)
References: UniProt: Q16539, mitogen-activated protein kinase
#2: Chemical ChemComp-A1A2O / 5-[(2,4-difluorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-1-(2-methylpropyl)-1H-indazole-6-carboxamide


Mass: 414.491 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H28F2N4O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GG5 / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE


Mass: 239.248 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H10FN3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 81 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.49 Å3/Da / Density % sol: 50.64 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 0.1M Ammonium Acetate, 0.1M BisTris (pH 5.5), 20% PEG 10,000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.8731 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Jul 14, 2023 / Details: Vertical CRL / Horizontal Eliptical mirror
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8731 Å / Relative weight: 1
ReflectionResolution: 1.973→54.616 Å / Num. obs: 23225 / % possible obs: 90 % / Redundancy: 13.9 % / Biso Wilson estimate: 37.97 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.122 / Rpim(I) all: 0.034 / Rrim(I) all: 0.127 / Net I/σ(I): 12.6
Reflection shellResolution: 1.973→2.233 Å / Redundancy: 13.8 % / Rmerge(I) obs: 1.668 / Mean I/σ(I) obs: 1.7 / Num. unique obs: 879 / CC1/2: 0.662 / Rpim(I) all: 0.468 / Rrim(I) all: 1.733 / % possible all: 60.7

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
autoPROC1.1.7data reduction
Aimless0.7.7data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.973→54.616 Å / SU ML: 0.2126 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 33.6912
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2573 864 4.92 %
Rwork0.2118 16701 -
obs0.214 17565 61.31 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 42.64 Å2
Refinement stepCycle: LAST / Resolution: 1.973→54.616 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2721 0 48 81 2850
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00262878
X-RAY DIFFRACTIONf_angle_d0.59983914
X-RAY DIFFRACTIONf_chiral_restr0.0403429
X-RAY DIFFRACTIONf_plane_restr0.0046510
X-RAY DIFFRACTIONf_dihedral_angle_d5.638403
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.973-2.10.599970.3423131X-RAY DIFFRACTION2.93
2.1-2.260.3654460.2914822X-RAY DIFFRACTION18.55
2.26-2.490.3471440.29052721X-RAY DIFFRACTION60.74
2.49-2.850.28742120.26584120X-RAY DIFFRACTION91.16
2.85-3.580.2662240.22764424X-RAY DIFFRACTION96.71
3.58-54.6160.22792310.17614483X-RAY DIFFRACTION94.72
Refinement TLS params.Method: refined / Origin x: 6.466939339 Å / Origin y: 3.96979149243 Å / Origin z: 16.0411186872 Å
111213212223313233
T0.0539786599954 Å20.0449946012911 Å20.00746125986405 Å2--0.0439963977417 Å20.175050863513 Å2---0.166236247024 Å2
L0.92382419423 °2-0.174404177059 °2-0.138558484455 °2-2.05117130328 °2-0.192694755525 °2--1.19364801311 °2
S0.205028493328 Å °-0.00400979647894 Å °-0.225341560799 Å °0.29293650569 Å °-0.249852589154 Å °0.445404074775 Å °-0.01305842928 Å °-0.04178927197 Å °-0.747455674848 Å °
Refinement TLS groupSelection details: all

+
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