[English] 日本語
Yorodumi
- PDB-4f9y: Human P38 alpha MAPK In Complex With a Novel and Selective Small ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4f9y
TitleHuman P38 alpha MAPK In Complex With a Novel and Selective Small Molecule Inhibitor
ComponentsMitogen-activated protein kinase 14MAPK14
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / protein kinase catalytic domain / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions ...positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions / cartilage condensation / cellular response to UV-B / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / positive regulation of muscle cell differentiation / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / Activation of the AP-1 family of transcription factors / ERK/MAPK targets / regulation of cytokine production involved in inflammatory response / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / MAP kinase kinase activity / response to dietary excess / response to muramyl dipeptide / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / mitogen-activated protein kinase / cellular response to vascular endothelial growth factor stimulus / positive regulation of myoblast differentiation / signal transduction in response to DNA damage / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / lipopolysaccharide-mediated signaling pathway / positive regulation of cardiac muscle cell proliferation / negative regulation of inflammatory response to antigenic stimulus / 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 / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / stem cell differentiation / positive regulation of glucose import / placenta development / NOD1/2 Signaling Pathway / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / platelet activation / cellular response to virus / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / osteoblast differentiation / ADP signalling through P2Y purinoceptor 1 / glucose metabolic process / positive regulation of reactive oxygen species metabolic process / chemotaxis / cellular senescence / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / protein phosphatase binding / secretory granule lumen / Oxidative Stress Induced Senescence / angiogenesis / Regulation of TP53 Activity through Phosphorylation / cellular response to lipopolysaccharide / 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 / glutamatergic synapse / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / 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. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain ...Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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
BETA-MERCAPTOETHANOL / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE / Chem-LM3 / DI(HYDROXYETHYL)ETHER / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.85 Å
AuthorsGrum-Tokars, V.L. / Minasov, G. / Anderson, W.F. / Watterson, D.M.
Funding support United States, 5items
OrganizationGrant numberCountry
Alzheimerss Drug Discovery Foundation (ADDF)261108 United States
National Institutes of Health/National Institute on Aging (NIH/NIA)U01AG043415 United States
National Institutes of Health/National Institute on Aging (NIH/NIA)R01AG031311 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS056051 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS093920 United States
CitationJournal: Plos One / Year: 2013
Title: Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction.
Authors: Watterson, D.M. / Grum-Tokars, V.L. / Roy, S.M. / Schavocky, J.P. / Bradaric, B.D. / Bachstetter, A.D. / Xing, B. / Dimayuga, E. / Saeed, F. / Zhang, H. / Staniszewski, A. / Pelletier, J.C. ...Authors: Watterson, D.M. / Grum-Tokars, V.L. / Roy, S.M. / Schavocky, J.P. / Bradaric, B.D. / Bachstetter, A.D. / Xing, B. / Dimayuga, E. / Saeed, F. / Zhang, H. / Staniszewski, A. / Pelletier, J.C. / Minasov, G. / Anderson, W.F. / Arancio, O. / Van Eldik, L.J.
History
DepositionMay 21, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 5, 2013Provider: repository / Type: Initial release
Revision 1.1Jun 12, 2013Group: Database references
Revision 1.2Jul 24, 2013Group: Database references
Revision 1.3Jan 1, 2020Group: Author supporting evidence / Database references / Derived calculations
Category: pdbx_audit_support / struct_conn / struct_ref_seq_dif
Item: _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details

-
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)45,0237
Polymers43,9561
Non-polymers1,0676
Water5,260292
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)66.529, 74.834, 78.270
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Mitogen-activated protein kinase 14 / MAPK14 / 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: 43955.906 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) / Strain (production host): BL21(DE3)pLysS
References: UniProt: Q16539, mitogen-activated protein kinase

-
Non-polymers , 5 types, 298 molecules

#2: Chemical ChemComp-GG5 / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE


Mass: 239.248 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H10FN3
#3: Chemical ChemComp-LM3 / N,N-dimethyl-6-(naphthalen-1-yl)-5-(pyridin-4-yl)pyridazin-3-amine


Mass: 326.394 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H18N4
#4: Chemical ChemComp-BME / BETA-MERCAPTOETHANOL / 2-Mercaptoethanol


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS
#5: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER / Diethylene glycol


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 292 / 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: 2.22 Å3/Da / Density % sol: 44.5 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 0.1M Ammonium Acetate, 0.1 M BIS-TRIS pH 5.5, 17% PEG 10000, VAPOR DIFFUSION, SITTING DROP, temperature 295K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97857 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 9, 2011 / Details: Beryllium lenses
RadiationMonochromator: DIAMOND / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 1.85→50 Å / Num. all: 34190 / Num. obs: 34190 / % possible obs: 99.9 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 7.3 % / Rmerge(I) obs: 0.039
Reflection shellResolution: 1.85→1.88 Å / Redundancy: 7.3 % / Rmerge(I) obs: 0.537 / Mean I/σ(I) obs: 3.81 / Num. unique all: 1669 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
HKL-2000data collection
PHASERphasing
REFMAC5.5.0102refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.85→33.76 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.954 / SU B: 5.152 / SU ML: 0.074 / Cross valid method: THROUGHOUT / ESU R: 0.131 / ESU R Free: 0.12 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.19999 1719 5.1 %RANDOM
Rwork0.1671 ---
obs0.16871 32278 99.9 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 29.036 Å2
Baniso -1Baniso -2Baniso -3
1--0.05 Å2-0 Å20 Å2
2---1.14 Å2-0 Å2
3---1.2 Å2
Refinement stepCycle: LAST / Resolution: 1.85→33.76 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2732 0 76 292 3100
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0223079
X-RAY DIFFRACTIONr_bond_other_d0.0010.022088
X-RAY DIFFRACTIONr_angle_refined_deg1.3641.9884199
X-RAY DIFFRACTIONr_angle_other_deg0.853.0015091
X-RAY DIFFRACTIONr_dihedral_angle_1_deg2.9825378
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.07823.944142
X-RAY DIFFRACTIONr_dihedral_angle_3_deg10.21715532
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.7361521
X-RAY DIFFRACTIONr_chiral_restr0.0860.2456
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0213469
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02646
X-RAY DIFFRACTIONr_mcbond_it1.2071.51818
X-RAY DIFFRACTIONr_mcbond_other0.3791.5715
X-RAY DIFFRACTIONr_mcangle_it2.08122978
X-RAY DIFFRACTIONr_scbond_it3.0931261
X-RAY DIFFRACTIONr_scangle_it4.7114.51220
LS refinement shellResolution: 1.85→1.898 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.264 126 -
Rwork0.214 2340 -
obs--99.92 %
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)
14.49880.7580.68056.4502-1.74413.9366-0.0285-0.33120.03820.49910.08870.4995-0.4008-0.2027-0.06020.1303-0.01080.05580.12860.08630.1484-16.4586-0.004321.415
22.2403-0.69250.50421.9659-1.40151.58130.0663-0.171-0.16240.1450.07030.2417-0.1405-0.1394-0.13650.0811-0.00780.00710.03780.0130.0365-6.3734.059414.0463
32.16730.4010.36322.3808-0.80931.56950.0683-0.0673-0.12470.0511-0.13640.05680.12190.05430.0680.0777-0.00320.00950.05110.02520.035510.7834-4.067718.0745
42.47420.8809-0.25132.9984-0.49121.82220.0712-0.17090.17190.2093-0.0627-0.0244-0.01390.0443-0.00850.039-0.0106-0.01120.0790.02170.033820.320910.953219.1273
51.6389-0.0765-0.13621.6851-0.31760.31340.0204-0.1545-0.11360.0556-0.1365-0.42120.02020.16370.11610.11590.0162-0.00330.15710.05720.119424.48291.936515.1032
62.6294-1.48790.28896.146-3.52673.47740.04510.1256-0.1027-0.3373-0.00020.21930.2618-0.0247-0.04490.11840.0324-0.03310.09410.00450.0222-8.16467.92492.3606
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A5 - 48
2X-RAY DIFFRACTION2A49 - 120
3X-RAY DIFFRACTION3A121 - 167
4X-RAY DIFFRACTION4A168 - 250
5X-RAY DIFFRACTION5A251 - 324
6X-RAY DIFFRACTION6A325 - 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