[English] 日本語
Yorodumi
- PDB-3nww: P38 Alpha kinase complexed with a 2-aminothiazol-5-yl-pyrimidine ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3nww
TitleP38 Alpha kinase complexed with a 2-aminothiazol-5-yl-pyrimidine based inhibitor
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / P38 MAP KINASE / SERINE/THREONINE-PROTEIN KINASE / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / positive regulation of myoblast fusion / cartilage condensation / stress-activated protein kinase signaling cascade / 3'-UTR-mediated mRNA stabilization / CD163 mediating an anti-inflammatory response / positive regulation of cyclase activity / response to dietary excess ...Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / positive regulation of myoblast fusion / cartilage condensation / stress-activated protein kinase signaling cascade / 3'-UTR-mediated mRNA stabilization / CD163 mediating an anti-inflammatory response / positive regulation of cyclase activity / response to dietary excess / positive regulation of myotube differentiation / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of muscle cell differentiation / cellular response to UV-B / mitogen-activated protein kinase p38 binding / Myogenesis / Platelet sensitization by LDL / NFAT protein binding / cellular response to lipoteichoic acid / regulation of cytokine production involved in inflammatory response / Activation of the AP-1 family of transcription factors / p38MAPK cascade / ERK/MAPK targets / MAP kinase kinase activity / Regulation of MITF-M-dependent genes involved in pigmentation / cellular response to vascular endothelial growth factor stimulus / MAP kinase activity / mitogen-activated protein kinase / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / RHO GTPases Activate NADPH Oxidases / negative regulation of hippo signaling / positive regulation of myoblast differentiation / osteoclast differentiation / positive regulation of interleukin-12 production / signal transduction in response to DNA damage / p38MAPK events / positive regulation of erythrocyte differentiation / tumor necrosis factor-mediated signaling pathway / cellular response to ionizing radiation / cellular response to virus / activated TAK1 mediates p38 MAPK activation / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt signaling pathway / platelet activation / bone development / response to insulin / cellular senescence / NOD1/2 Signaling Pathway / VEGFA-VEGFR2 Pathway / osteoblast differentiation / positive regulation of reactive oxygen species metabolic process / chemotaxis / spindle pole / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / MAPK cascade / ADP signalling through P2Y purinoceptor 1 / cellular response to lipopolysaccharide / secretory granule lumen / protein phosphatase binding / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / ficolin-1-rich granule lumen / cell surface receptor signaling pathway / nuclear speck / intracellular signal transduction / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / positive regulation of gene expression / regulation of transcription by RNA polymerase II / Neutrophil degranulation / glutamatergic synapse / enzyme binding / signal transduction / mitochondrion / DNA-templated transcription / extracellular region / 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-3NW / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.09 Å
AuthorsSack, J.S.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38alpha MAP kinase inhibitors.
Authors: Lin, S. / Wrobleski, S.T. / Hynes, J. / Pitt, S. / Zhang, R. / Fan, Y. / Doweyko, A.M. / Kish, K.F. / Sack, J.S. / Malley, M.F. / Kiefer, S.E. / Newitt, J.A. / McKinnon, M. / Trzaskos, J. / ...Authors: Lin, S. / Wrobleski, S.T. / Hynes, J. / Pitt, S. / Zhang, R. / Fan, Y. / Doweyko, A.M. / Kish, K.F. / Sack, J.S. / Malley, M.F. / Kiefer, S.E. / Newitt, J.A. / McKinnon, M. / Trzaskos, J. / Barrish, J.C. / Dodd, J.H. / Schieven, G.L. / Leftheris, K.
History
DepositionJul 12, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 8, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jun 19, 2013Group: Database references
Revision 1.3Sep 2, 2020Group: Database references / Derived calculations / Structure summary
Category: struct_keywords / struct_ref_seq_dif / struct_site
Item: _struct_keywords.text / _struct_ref_seq_dif.details ..._struct_keywords.text / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Feb 21, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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)42,5882
Polymers42,1051
Non-polymers4831
Water3,765209
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)66.155, 75.055, 78.628
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 / MAP kinase 14 / MAPK 14 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha / ...MAP kinase 14 / MAPK 14 / 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: 42105.004 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 / Cell line (production host): BL21(DE3) / Production host: Escherichia coli (E. coli)
References: UniProt: Q16539, mitogen-activated protein kinase
#2: Chemical ChemComp-3NW / 1-[2-(2-{[2-(dimethylamino)ethyl]amino}-6-{2-[(1-methylethyl)amino]-1,3-thiazol-5-yl}pyrimidin-4-yl)benzyl]-3-ethylurea


Mass: 482.645 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H34N8OS
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 209 / 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: 2.32 Å3/Da / Density % sol: 46.94 %

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418
DetectorType: RIGAKU SATURN 92 / Detector: CCD / Date: Jul 20, 2005 / Details: MICROMAX CONFOCAL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2→78.64 Å / Num. obs: 24028 / % possible obs: 90 % / Observed criterion σ(I): 0 / Redundancy: 7.2 % / Biso Wilson estimate: 36.97 Å2 / Rmerge(I) obs: 0.059 / Net I/σ(I): 24.6
Reflection shellResolution: 2→2.11 Å / Redundancy: 6.3 % / Rmerge(I) obs: 0.473 / Mean I/σ(I) obs: 3.8 / % possible all: 57.5

-
Processing

Software
NameVersionClassification
BUSTER2.9.3refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.09→22.9 Å / Cor.coef. Fo:Fc: 0.9457 / Cor.coef. Fo:Fc free: 0.9311 / SU R Cruickshank DPI: 0.24 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2544 1158 5.16 %RANDOM
Rwork0.2115 ---
obs0.2137 22432 94.36 %-
Displacement parametersBiso mean: 40.46 Å2
Baniso -1Baniso -2Baniso -3
1--5.7777 Å20 Å20 Å2
2--7.1389 Å20 Å2
3----1.3612 Å2
Refine analyzeLuzzati coordinate error obs: 0.298 Å
Refinement stepCycle: LAST / Resolution: 2.09→22.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2741 0 34 209 2984
Refine LS restraints
Refine-IDTypeDev idealNumberWeight
X-RAY DIFFRACTIONt_bond_d0.0128412
X-RAY DIFFRACTIONt_angle_deg1.0938552
X-RAY DIFFRACTIONt_dihedral_angle_d9792
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes692
X-RAY DIFFRACTIONt_gen_planes4045
X-RAY DIFFRACTIONt_it284120
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.05
X-RAY DIFFRACTIONt_other_torsion19.34
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion3645
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact34534
LS refinement shellResolution: 2.09→2.19 Å / Total num. of bins used: 11
RfactorNum. reflection% reflection
Rfree0.2436 116 4.83 %
Rwork0.2145 2287 -
all0.2158 2403 -
obs--94.36 %

+
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