[English] 日本語
Yorodumi
- PDB-3mvl: P38 Alpha Map Kinase complexed with pyrrolotriazine inhibitor 7K -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3mvl
TitleP38 Alpha Map Kinase complexed with pyrrolotriazine inhibitor 7K
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / SERINE/THREONINE-PROTEIN KINASE / KINASE / P38 MAP 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 / ERK/MAPK targets / p38MAPK cascade / 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-38P / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsSack, J.S.
CitationJournal: J.Med.Chem. / Year: 2010
Title: Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-Methylphenylamino)-5-Methyl-Npropylpyrrolo[1,2-F][1,2,4] Triazine-6-Carboxamide (Bms-582949), a Clinical P38 Map Kinase Inhibitor for the Treatment ...Title: Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-Methylphenylamino)-5-Methyl-Npropylpyrrolo[1,2-F][1,2,4] Triazine-6-Carboxamide (Bms-582949), a Clinical P38 Map Kinase Inhibitor for the Treatment of Inflammatory Diseases
Authors: Liu, C. / Lin, J. / Wrobleski, S.T. / Lin, S. / Hynes, J. / Wu, H. / Dyckman, A.J. / Li, T. / Wityak, J. / Gillooly, K.M. / Pitt, S. / Shen, D.R. / Zhang, R.F. / McIntyre, K.W. / Salter-Cid, ...Authors: Liu, C. / Lin, J. / Wrobleski, S.T. / Lin, S. / Hynes, J. / Wu, H. / Dyckman, A.J. / Li, T. / Wityak, J. / Gillooly, K.M. / Pitt, S. / Shen, D.R. / Zhang, R.F. / McIntyre, K.W. / Salter-Cid, L. / Shuster, D.J. / Zhang, H. / Marathe, P.H. / Doweyko, A.M. / Sack, J.S. / Kiefer, S.E. / Kish, K.F. / Newitt, J.A. / McKinnon, M. / Dodd, J.H. / Barrish, J.C. / Schieven, G.L. / Leftheris, K.
History
DepositionMay 4, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 13, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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
B: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)85,0234
Polymers84,2102
Non-polymers8132
Water2,252125
1
A: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,5112
Polymers42,1051
Non-polymers4061
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,5112
Polymers42,1051
Non-polymers4061
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)67.540, 71.680, 72.820
Angle α, β, γ (deg.)90.00, 90.01, 90.00
Int Tables number4
Space group name H-MP1211

-
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.: 2
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-38P / 4-{[5-(cyclopropylcarbamoyl)-2-methylphenyl]amino}-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide


Mass: 406.481 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H26N6O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 125 / 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: 2.09 Å3/Da / Density % sol: 41.24 %

-
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: May 28, 2002 / Details: MICROMAX CONFOCAL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.8→40.75 Å / Num. obs: 17200 / % possible obs: 99.5 % / Observed criterion σ(I): 0 / Redundancy: 4.2 % / Biso Wilson estimate: 49.51 Å2 / Rmerge(I) obs: 0.041 / Net I/σ(I): 31.5
Reflection shellResolution: 2.8→2.95 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.124 / Mean I/σ(I) obs: 12 / % possible all: 97.2

-
Processing

Software
NameVersionClassification
BUSTER2.9.4refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.8→33.77 Å / Cor.coef. Fo:Fc: 0.8028 / Cor.coef. Fo:Fc free: 0.6036 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.3349 871 5.06 %RANDOM
Rwork0.2272 ---
obs0.2326 17198 99.42 %-
Displacement parametersBiso mean: 30.17 Å2
Baniso -1Baniso -2Baniso -3
1-4.9465 Å20 Å20.9446 Å2
2--5.0893 Å20 Å2
3----10.0358 Å2
Refine analyzeLuzzati coordinate error obs: 0.399 Å
Refinement stepCycle: LAST / Resolution: 2.8→33.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5482 0 60 125 5667
Refine LS restraints
Refine-IDTypeDev idealNumberWeight
X-RAY DIFFRACTIONt_bond_d0.0156762
X-RAY DIFFRACTIONt_angle_deg1.2577082
X-RAY DIFFRACTIONt_dihedral_angle_d19582
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes1382
X-RAY DIFFRACTIONt_gen_planes8085
X-RAY DIFFRACTIONt_it567620
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.64
X-RAY DIFFRACTIONt_other_torsion24.42
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion7285
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_contact65704
LS refinement shellResolution: 2.8→2.97 Å / Total num. of bins used: 9
RfactorNum. reflection% reflection
Rfree0.3508 140 5.22 %
Rwork0.2315 2543 -
all0.2382 2683 -
obs--99.42 %

+
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