[English] 日本語
Yorodumi
- PDB-3hl7: Crystal Structure of Human p38alpha complexed with SD-0006 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3hl7
TitleCrystal Structure of Human p38alpha complexed with SD-0006
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / ATP-binding / Kinase / Nucleotide-binding / Nucleus / Phosphoprotein / Serine/threonine-protein kinase
Function / homology
Function and homology information


stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / 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 / cartilage condensation ...stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / 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 / cartilage condensation / positive regulation of myoblast fusion / cellular response to UV-B / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / positive regulation of muscle cell differentiation / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / D-glucose import / regulation of cytokine production involved in inflammatory response / 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 / MAP kinase activity / RHO GTPases Activate NADPH Oxidases / regulation of ossification / cellular response to vascular endothelial growth factor stimulus / signal transduction in response to DNA damage / mitogen-activated protein kinase / negative regulation of hippo signaling / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / positive regulation of cardiac muscle cell proliferation / skeletal muscle tissue development / lipopolysaccharide-mediated signaling pathway / 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 / positive regulation of D-glucose import / stem cell differentiation / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / negative regulation of inflammatory response to antigenic stimulus / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / placenta development / NOD1/2 Signaling Pathway / cellular response to virus / platelet activation / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / osteoblast differentiation / glucose metabolic process / ADP signalling through P2Y purinoceptor 1 / chemotaxis / positive regulation of reactive oxygen species metabolic process / cellular senescence / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / angiogenesis / secretory granule lumen / Oxidative Stress Induced Senescence / 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 / glutamatergic synapse / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / apoptotic process / 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 ...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
Chem-I46 / Chem-I47 / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.88 Å
AuthorsShieh, H.-S. / Kurumbail, R.G. / Stegeman, R.A. / Williams, J.M.
CitationJournal: Biochemistry / Year: 2009
Title: Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804.
Authors: Xing, L. / Shieh, H.S. / Selness, S.R. / Devraj, R.V. / Walker, J.K. / Devadas, B. / Hope, H.R. / Compton, R.P. / Schindler, J.F. / Hirsch, J.L. / Benson, A.G. / Kurumbail, R.G. / Stegeman, ...Authors: Xing, L. / Shieh, H.S. / Selness, S.R. / Devraj, R.V. / Walker, J.K. / Devadas, B. / Hope, H.R. / Compton, R.P. / Schindler, J.F. / Hirsch, J.L. / Benson, A.G. / Kurumbail, R.G. / Stegeman, R.A. / Williams, J.M. / Broadus, R.M. / Walden, Z. / Monahan, J.B.
History
DepositionMay 26, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 14, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Revision 1.3Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)41,9983
Polymers41,3431
Non-polymers6552
Water4,666259
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.088, 74.525, 77.587
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 alpha / MAP kinase p38 alpha / Cytokine suppressive anti- ...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: 41343.195 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, THP-1 / Plasmid: pGEX4T-1 / Production host: Escherichia coli (E. coli) / Strain (production host): DH10B
References: UniProt: Q16539, mitogen-activated protein kinase
#2: Chemical ChemComp-I47 / 2-{4-[5-(4-chlorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxoethanol


Mass: 397.858 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20ClN5O2
#3: Chemical ChemComp-I46 / 2-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridine


Mass: 257.238 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H9F2N3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 259 / 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: 2.28 Å3/Da / Density % sol: 45.95 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 9
Details: 20-30% PEG3000, 10 mM CaCl2, 50 mM CHES, pH 9.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Apr 5, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.88→40 Å / Num. all: 30715 / Num. obs: 30175 / % possible obs: 100 % / Observed criterion σ(F): -1.5 / Observed criterion σ(I): -3 / Redundancy: 6.5 % / Biso Wilson estimate: 28.3 Å2 / Rmerge(I) obs: 0.054 / Rsym value: 0.054 / Net I/σ(I): 34.6
Reflection shellResolution: 1.88→1.97 Å / Redundancy: 4.5 % / Rmerge(I) obs: 0.454 / Mean I/σ(I) obs: 2.5 / Num. unique all: 2405 / Rsym value: 0.454 / % possible all: 77.5

-
Processing

Software
NameVersionClassification
HKL-2000data collection
REFMAC5.2.0019refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.88→24.84 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.941 / SU B: 7.017 / SU ML: 0.109 / TLS residual ADP flag: LIKELY RESIDUAL / Isotropic thermal model: restrained individual isotropic / Cross valid method: THROUGHOUT / ESU R: 0.16 / ESU R Free: 0.141 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22825 1547 5 %RANDOM
Rwork0.19858 ---
obs0.20006 29122 98.42 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 29.233 Å2
Baniso -1Baniso -2Baniso -3
1-0.01 Å20 Å20 Å2
2---1.19 Å20 Å2
3---1.18 Å2
Refinement stepCycle: LAST / Resolution: 1.88→24.84 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2698 0 47 259 3004
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0222813
X-RAY DIFFRACTIONr_bond_other_d0.0010.021865
X-RAY DIFFRACTIONr_angle_refined_deg1.2851.9823821
X-RAY DIFFRACTIONr_angle_other_deg0.89834553
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.3395334
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.93524.141128
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.68415478
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.7651516
X-RAY DIFFRACTIONr_chiral_restr0.0760.2423
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.023147
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02550
X-RAY DIFFRACTIONr_nbd_refined0.2080.2649
X-RAY DIFFRACTIONr_nbd_other0.1880.21953
X-RAY DIFFRACTIONr_nbtor_refined0.1880.21389
X-RAY DIFFRACTIONr_nbtor_other0.0890.21406
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.170.2186
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1090.216
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2080.241
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1290.211
X-RAY DIFFRACTIONr_mcbond_it0.7311.51713
X-RAY DIFFRACTIONr_mcbond_other0.1351.5671
X-RAY DIFFRACTIONr_mcangle_it1.22922722
X-RAY DIFFRACTIONr_scbond_it1.6631229
X-RAY DIFFRACTIONr_scangle_it2.5224.51099
LS refinement shellResolution: 1.88→1.933 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.327 88 -
Rwork0.245 1780 -
obs--81.75 %
Refinement TLS params.Method: refined / Origin x: 25.8924 Å / Origin y: 33.8746 Å / Origin z: 15.6439 Å
111213212223313233
T-0.1066 Å20.0204 Å2-0.0365 Å2--0.1878 Å2-0.0363 Å2---0.2379 Å2
L3.5555 °20.0056 °2-0.2605 °2-1.4505 °20.464 °2--0.9331 °2
S0.0126 Å °-0.1545 Å °-0.0092 Å °0.1142 Å °-0.0361 Å °-0.0817 Å °0.0352 Å °-0.0249 Å °0.0235 Å °

+
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