[English] 日本語
Yorodumi
- PDB-7z6i: Crystal structure of p38alpha C162S in complex with SB20358 and C... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7z6i
TitleCrystal structure of p38alpha C162S in complex with SB20358 and CAS 2094667-81-7 (behind catalytic site; Y35 in), P 21 21 21
ComponentsMitogen-activated protein kinase 14MAPK14
KeywordsONCOPROTEIN / kinase / enzyme / inhibitor / ligand
Function / homology
Function and homology information


DSCAM interactions / p38MAPK events / Activation of the AP-1 family of transcription factors / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / ERK/MAPK targets / activated TAK1 mediates p38 MAPK activation / NOD1/2 Signaling Pathway / ADP signalling through P2Y purinoceptor 1 / Oxidative Stress Induced Senescence ...DSCAM interactions / p38MAPK events / Activation of the AP-1 family of transcription factors / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / ERK/MAPK targets / activated TAK1 mediates p38 MAPK activation / NOD1/2 Signaling Pathway / ADP signalling through P2Y purinoceptor 1 / Oxidative Stress Induced Senescence / 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 / cartilage condensation / cellular response to UV-B / stress-activated protein kinase signaling cascade / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / glucose import / regulation of cytokine production involved in inflammatory response / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / response to dietary excess / response to muramyl dipeptide / regulation of ossification / MAP kinase activity / mitogen-activated protein kinase / cellular response to vascular endothelial growth factor stimulus / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / signal transduction in response to DNA damage / lipopolysaccharide-mediated signaling pathway / positive regulation of cardiac muscle cell proliferation / striated muscle cell differentiation / response to muscle stretch / positive regulation of brown fat cell differentiation / Neutrophil degranulation / positive regulation of interleukin-12 production / osteoclast differentiation / positive regulation of erythrocyte differentiation / placenta development / DNA damage checkpoint signaling / cellular response to ionizing radiation / stem cell differentiation / positive regulation of glucose import / response to insulin / bone development / cell morphogenesis / negative regulation of canonical Wnt signaling pathway / cellular response to virus / osteoblast differentiation / spindle pole / positive regulation of protein import into nucleus / glucose metabolic process / positive regulation of reactive oxygen species metabolic process / MAPK cascade / cellular response to tumor necrosis factor / kinase activity / peptidyl-serine phosphorylation / protein phosphatase binding / angiogenesis / cellular response to lipopolysaccharide / 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 / glutamatergic synapse / apoptotic process / DNA damage response / positive regulation of gene expression / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / enzyme binding / 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. / 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
Chem-87B / Chem-IIM / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.25 Å
AuthorsBaginski, B. / Pous, J. / Gonzalez, L. / Macias, M.J. / Nebreda, A.R.
Funding support Spain, 2items
OrganizationGrant numberCountry
Spanish Ministry of Science, Innovation, and UniversitiesPID2019-109521RB-100 Spain
La Caixa FoundationBioMedTec VIII - Nebre Spain
CitationJournal: Nat Commun / Year: 2023
Title: Characterization of p38 alpha autophosphorylation inhibitors that target the non-canonical activation pathway.
Authors: Gonzalez, L. / Diaz, L. / Pous, J. / Baginski, B. / Duran-Corbera, A. / Scarpa, M. / Brun-Heath, I. / Igea, A. / Martin-Malpartida, P. / Ruiz, L. / Pallara, C. / Esguerra, M. / Colizzi, F. / ...Authors: Gonzalez, L. / Diaz, L. / Pous, J. / Baginski, B. / Duran-Corbera, A. / Scarpa, M. / Brun-Heath, I. / Igea, A. / Martin-Malpartida, P. / Ruiz, L. / Pallara, C. / Esguerra, M. / Colizzi, F. / Mayor-Ruiz, C. / Biondi, R.M. / Soliva, R. / Macias, M.J. / Orozco, M. / Nebreda, A.R.
History
DepositionMar 11, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 14, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 21, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Feb 7, 2024Group: 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
AAA: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,0683
Polymers41,3631
Non-polymers7052
Water3,603200
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area16800 Å2
Unit cell
Length a, b, c (Å)65.142, 74.570, 77.550
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Mitogen-activated protein kinase 14 / MAPK14 / MAP kinase 14 / MAPK 14 / CRK1 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha


Mass: 41363.148 Da / Num. of mol.: 1 / Mutation: C162S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Mapk14, Crk1, Csbp1, Csbp2 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P47811, mitogen-activated protein kinase
#2: Chemical ChemComp-IIM / 4-[4-(4-fluorophenyl)-2-[4-[methyl(oxidanyl)-$l^{3}-sulfanyl]phenyl]-1~{H}-imidazol-5-yl]pyridine


Mass: 377.435 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H16FN3OS
#3: Chemical ChemComp-87B / N-(2-cyclobutyl-1H-1,3-benzodiazol-5-yl)benzenesulfonamide


Mass: 327.401 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H17N3O2S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 200 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.35 Å3/Da / Density % sol: 47.62 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 0.087 M Ca Acetate 0.1M MES pH 6.0 7.1% PEG 550MME

-
Data collection

DiffractionMean temperature: 100 K / Ambient temp details: oxford Cryo 700 / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALBA / Beamline: XALOC / Wavelength: 0.9793 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 16, 2020 / Details: Elliptically bent mirror
RadiationMonochromator: Si(111) channel-cut, cryocooled / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9793 Å / Relative weight: 1
ReflectionResolution: 2.25→77.55 Å / Num. obs: 18525 / % possible obs: 100 % / Redundancy: 5.6 % / Biso Wilson estimate: 28.9 Å2 / Rmerge(I) obs: 0.092 / Net I/σ(I): 16.5
Reflection shellResolution: 2.25→2.37 Å / Redundancy: 5.6 % / Rmerge(I) obs: 0.451 / Mean I/σ(I) obs: 9.2 / Num. unique obs: 2625 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.8.0403refinement
autoPROC1.0.5data reduction
SCALA3.3.22data scaling
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4LOO

4loo


Resolution: 2.25→53.752 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.914 / WRfactor Rfree: 0.267 / WRfactor Rwork: 0.211 / SU B: 6.485 / SU ML: 0.164 / Average fsc free: 0.9574 / Average fsc work: 0.9748 / Cross valid method: FREE R-VALUE / ESU R: 0.318 / ESU R Free: 0.233
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflectionSelection details
Rfree0.2479 884 4.784 %random
Rwork0.1929 17596 --
all0.195 ---
obs-18480 99.957 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK
Displacement parametersBiso mean: 36.604 Å2
Baniso -1Baniso -2Baniso -3
1--0.918 Å2-0 Å2-0 Å2
2---1.492 Å20 Å2
3---2.409 Å2
Refinement stepCycle: LAST / Resolution: 2.25→53.752 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2824 0 50 200 3074
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0030.0122843
X-RAY DIFFRACTIONr_bond_other_d0.0010.0162685
X-RAY DIFFRACTIONr_angle_refined_deg1.1821.6593872
X-RAY DIFFRACTIONr_angle_other_deg0.4091.5836161
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7215343
X-RAY DIFFRACTIONr_dihedral_angle_2_deg4.757520
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.39910472
X-RAY DIFFRACTIONr_dihedral_angle_6_deg13.86710134
X-RAY DIFFRACTIONr_chiral_restr0.0480.2427
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.023316
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02675
X-RAY DIFFRACTIONr_nbd_refined0.2140.2567
X-RAY DIFFRACTIONr_symmetry_nbd_other0.2070.22472
X-RAY DIFFRACTIONr_nbtor_refined0.180.21402
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0770.21411
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1610.2159
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.050.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1460.211
X-RAY DIFFRACTIONr_nbd_other0.1780.242
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.160.23
X-RAY DIFFRACTIONr_mcbond_it2.2573.9951349
X-RAY DIFFRACTIONr_mcbond_other2.2553.9961349
X-RAY DIFFRACTIONr_mcangle_it3.8137.1671684
X-RAY DIFFRACTIONr_mcangle_other3.8127.1691685
X-RAY DIFFRACTIONr_scbond_it2.3044.2571494
X-RAY DIFFRACTIONr_scbond_other2.3044.2591495
X-RAY DIFFRACTIONr_scangle_it3.9687.7082181
X-RAY DIFFRACTIONr_scangle_other3.9677.712182
X-RAY DIFFRACTIONr_lrange_it6.40540.0673281
X-RAY DIFFRACTIONr_lrange_other6.32939.8773246
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.25-2.3080.276600.20912580.21313190.9520.9799.92420.193
2.308-2.3710.244670.21412320.21612990.9590.9671000.203
2.371-2.440.272670.20912070.21312740.9420.971000.199
2.44-2.5150.294560.2111960.21412520.9430.9691000.204
2.515-2.5970.244740.20311260.20512000.9560.9741000.201
2.597-2.6880.289550.211060.20411640.9490.97499.74230.201
2.688-2.7890.26600.18210510.18511110.9560.9781000.181
2.789-2.9030.252450.17510550.17811010.9690.9899.90920.182
2.903-3.0320.235460.189820.18210280.9660.9781000.189
3.032-3.1790.24410.1859630.18610040.9650.9771000.198
3.179-3.3510.211460.1899070.199530.9710.9771000.204
3.351-3.5530.262420.1998710.2029130.9480.9741000.222
3.553-3.7970.267460.1768050.188510.960.9811000.2
3.797-4.10.223340.1687710.178060.970.98299.87590.201
4.1-4.4880.268320.1677070.177390.9660.9821000.202
4.488-5.0140.238240.1736520.1756770.9570.98199.85230.216
5.014-5.7810.164230.2255760.2225990.9830.9721000.269
5.781-7.060.306270.2284960.2325230.9410.9711000.284
7.06-9.8990.262190.1883960.1914160.9520.97899.75960.247
9.899-53.7520.214200.2842390.2782590.9780.951000.353

+
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