[English] 日本語
Yorodumi
- PDB-3kga: Crystal structure of MAPKAP kinase 2 (MK2) complexed with a poten... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3kga
TitleCrystal structure of MAPKAP kinase 2 (MK2) complexed with a potent 3-aminopyrazole ATP site inhibitor
ComponentsMAP kinase-activated protein kinase 2
KeywordsTRANSFERASE / Small molecule inhibitor / 3-aminopyrazole scaffold / Scaffold hoping / ATP-site kinase inhibitor / Induced fit / Novel hydrophobic pocket / Activation loop deletion / Alternative splicing / ATP-binding / Kinase / Nucleotide-binding / Phosphoprotein / Polymorphism / Serine/threonine-protein kinase
Function / homology
Function and homology information


macropinocytosis / CREB phosphorylation / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / leukotriene metabolic process / calcium-dependent protein serine/threonine kinase activity / Synthesis of Leukotrienes (LT) and Eoxins (EX) / regulation of tumor necrosis factor production / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of macrophage cytokine production ...macropinocytosis / CREB phosphorylation / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / leukotriene metabolic process / calcium-dependent protein serine/threonine kinase activity / Synthesis of Leukotrienes (LT) and Eoxins (EX) / regulation of tumor necrosis factor production / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of macrophage cytokine production / mitogen-activated protein kinase binding / regulation of interleukin-6 production / calmodulin-dependent protein kinase activity / 3'-UTR-mediated mRNA stabilization / toll-like receptor signaling pathway / p38MAPK cascade / inner ear development / Regulation of HSF1-mediated heat shock response / cellular response to vascular endothelial growth factor stimulus / vascular endothelial growth factor receptor signaling pathway / regulation of cellular response to heat / p38MAPK events / regulation of mRNA stability / response to cytokine / activated TAK1 mediates p38 MAPK activation / Regulation of TNFR1 signaling / VEGFA-VEGFR2 Pathway / positive regulation of tumor necrosis factor production / MAPK cascade / peptidyl-serine phosphorylation / Oxidative Stress Induced Senescence / response to lipopolysaccharide / calmodulin binding / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / inflammatory response / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA damage response / extracellular exosome / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
MAP kinase activated protein kinase, C-terminal / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site ...MAP kinase activated protein kinase, C-terminal / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-LX9 / MAP kinase-activated protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.55 Å
AuthorsKroemer, M. / Velcicky, J. / Izaac, A. / Be, C. / Huppertz, C. / Pflieger, D. / Schlapbach, A. / Scheufler, C.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy.
Authors: Velcicky, J. / Feifel, R. / Hawtin, S. / Heng, R. / Huppertz, C. / Koch, G. / Kroemer, M. / Moebitz, H. / Revesz, L. / Scheufler, C. / Schlapbach, A.
History
DepositionOct 28, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 26, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 13, 2021Group: Database references / Derived calculations
Category: database_2 / pdbx_struct_conn_angle ...database_2 / pdbx_struct_conn_angle / struct_conn / 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 / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Feb 21, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: MAP kinase-activated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,0083
Polymers34,5641
Non-polymers4442
Water1,802100
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)103.120, 103.120, 165.415
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number182
Space group name H-MP6322

-
Components

#1: Protein MAP kinase-activated protein kinase 2 / MAPK-activated protein kinase 2 / MAPKAP kinase 2 / MAPKAPK-2 / MK2


Mass: 34564.043 Da / Num. of mol.: 1 / Fragment: Kinase domain / Mutation: DELTA216-236, P237G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPKAPK2 / Plasmid: pET / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)Tuner
References: UniProt: P49137, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#3: Chemical ChemComp-LX9 / 6-{3-amino-1-[3-(1H-indol-6-yl)phenyl]-1H-pyrazol-4-yl}-3,4-dihydroisoquinolin-1(2H)-one


Mass: 419.478 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H21N5O
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 100 / 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: 3.67 Å3/Da / Density % sol: 66.51 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.3
Details: 0.1M BICINE, 1.3M SODIUM MALONATE, pH 8.3, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.9999 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Nov 30, 2007
RadiationMonochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 2.55→30 Å / Num. all: 17605 / Num. obs: 17605 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 7.7 % / Biso Wilson estimate: 37.6 Å2 / Rmerge(I) obs: 0.108 / Net I/σ(I): 17.1
Reflection shellResolution: 2.55→2.66 Å / Redundancy: 7.7 % / Rmerge(I) obs: 0.526 / Mean I/σ(I) obs: 3.9 / Num. unique all: 1967 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.3.0040refinement
XDSdata reduction
XSCALEdata scaling
REFMAC5.3.0040phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.55→29.3 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.907 / SU B: 7.121 / SU ML: 0.157 / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / ESU R: 0.28 / ESU R Free: 0.234 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.23459 881 5 %RANDOM
Rwork0.18002 ---
obs0.18274 16723 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 35.071 Å2
Baniso -1Baniso -2Baniso -3
1--1.16 Å2-0.58 Å20 Å2
2---1.16 Å20 Å2
3---1.73 Å2
Refinement stepCycle: LAST / Resolution: 2.55→29.3 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2333 0 33 100 2466
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0222419
X-RAY DIFFRACTIONr_angle_refined_deg1.5031.9813272
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1025294
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.17223.922102
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.59115435
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.4351515
X-RAY DIFFRACTIONr_chiral_restr0.0930.2357
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.021806
X-RAY DIFFRACTIONr_nbd_refined0.2360.3995
X-RAY DIFFRACTIONr_nbtor_refined0.3320.51620
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1870.5218
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2150.340
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2210.58
X-RAY DIFFRACTIONr_mcbond_it2.01121515
X-RAY DIFFRACTIONr_mcangle_it3.24332375
X-RAY DIFFRACTIONr_scbond_it4.9334.51045
X-RAY DIFFRACTIONr_scangle_it7.0816897
LS refinement shellResolution: 2.55→2.639 Å / Rfactor Rfree error: 0.234 / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.318 85 -
Rwork0.241 1598 -
obs-1598 99.94 %

+
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