[English] 日本語
Yorodumi
- PDB-6yg2: Crystal structure of MKK7 (MAP2K7) in complex with ibrutnib, with... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6yg2
TitleCrystal structure of MKK7 (MAP2K7) in complex with ibrutnib, with covalent and allosteric binding modes
ComponentsDual specificity mitogen-activated protein kinase kinase 7
KeywordsTRANSFERASE / kinase / kinase inhibitor / MKK7 / MEK7 / MAP2K7 / MAP2K / MEK / JNK signaling / Structural Genomics / Structural Genomics Consortium / SGC
Function / homology
Function and homology information


JUN kinase kinase activity / regulation of motor neuron apoptotic process / mitogen-activated protein kinase kinase / response to osmotic stress / Fc-epsilon receptor signaling pathway / positive regulation of telomere maintenance / MAP kinase kinase activity / response to tumor necrosis factor / Uptake and function of anthrax toxins / MAP kinase activity ...JUN kinase kinase activity / regulation of motor neuron apoptotic process / mitogen-activated protein kinase kinase / response to osmotic stress / Fc-epsilon receptor signaling pathway / positive regulation of telomere maintenance / MAP kinase kinase activity / response to tumor necrosis factor / Uptake and function of anthrax toxins / MAP kinase activity / cellular response to interleukin-1 / stress-activated MAPK cascade / response to UV / JNK cascade / molecular function activator activity / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of JNK cascade / FCERI mediated MAPK activation / response to wounding / cellular senescence / cellular response to lipopolysaccharide / response to heat / protein tyrosine kinase activity / protein phosphatase binding / Oxidative Stress Induced Senescence / positive regulation of ERK1 and ERK2 cascade / protein serine kinase activity / apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / enzyme binding / magnesium ion binding / signal transduction / ATP binding / nucleus / cytoplasm / cytosol
Similarity search - Function
: / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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 domain profile. ...: / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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 domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-1E8 / Chem-8E8 / Dual specificity mitogen-activated protein kinase kinase 7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsChaikuad, A. / Knapp, S. / Structural Genomics Consortium (SGC)
CitationJournal: Cell Chem Biol / Year: 2020
Title: Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities.
Authors: Schroder, M. / Tan, L. / Wang, J. / Liang, Y. / Gray, N.S. / Knapp, S. / Chaikuad, A.
History
DepositionMar 27, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 12, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 28, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dual specificity mitogen-activated protein kinase kinase 7
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,63715
Polymers34,9451
Non-polymers1,69214
Water3,279182
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2260 Å2
ΔGint31 kcal/mol
Surface area14670 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.111, 74.955, 86.666
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Dual specificity mitogen-activated protein kinase kinase 7 / MAPKK 7 / JNK-activating kinase 2 / MAPK/ERK kinase 7 / MEK 7 / Stress-activated protein kinase ...MAPKK 7 / JNK-activating kinase 2 / MAPK/ERK kinase 7 / MEK 7 / Stress-activated protein kinase kinase 4 / SAPKK4 / c-Jun N-terminal kinase kinase 2 / JNKK 2


Mass: 34944.621 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K7, JNKK2, MEK7, MKK7, PRKMK7, SKK4 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): -R3-pRARE2
References: UniProt: O14733, mitogen-activated protein kinase kinase

-
Non-polymers , 5 types, 196 molecules

#2: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-1E8 / 1-{(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}prop-2-en-1-one / Imbruvica / PCI-32765


Mass: 440.497 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H24N6O2 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-8E8 / 1-[(3~{R})-3-[4-azanyl-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]propan-1-one / Ibrutinib (bound form)


Mass: 442.513 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H26N6O2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 182 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50.17 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 7.8
Details: 19% PEG3350, 0.1 M ammonium acetate, 0.1 M tris, pH 7.8

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 1.02823 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 13, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.02823 Å / Relative weight: 1
ReflectionResolution: 2→19.55 Å / Num. obs: 24057 / % possible obs: 99.9 % / Redundancy: 7.3 % / CC1/2: 0.997 / Rmerge(I) obs: 0.106 / Rpim(I) all: 0.042 / Rrim(I) all: 0.115 / Net I/av σ(I): 5.8 / Net I/σ(I): 12.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allRsym value% possible all
2-2.117.40.9010.834730.9010.3510.9680.901100
2.11-2.247.30.5571.432520.2190.5990.557100
2.24-2.397.30.381230800.1510.410.381100
2.39-2.587.30.262.928950.1030.280.26100
2.58-2.837.40.1714.426520.0670.1840.171100
2.83-3.167.40.1156.324320.0450.1230.115100
3.16-3.657.30.079.221390.0280.0760.07100
3.65-4.477.20.0511.718480.020.0540.05100
4.47-6.3270.04512.114610.0190.0490.045100
6.32-19.386.50.045118250.020.050.04596.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0073refinement
SCALA3.3.21data scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2dyl

2dyl


Resolution: 2→19.55 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.934 / SU B: 7.917 / SU ML: 0.115 / SU R Cruickshank DPI: 0.1682 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.168 / ESU R Free: 0.159
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2304 1176 4.9 %RANDOM
Rwork0.1789 ---
obs0.1815 22831 99.84 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 114.25 Å2 / Biso mean: 38.529 Å2 / Biso min: 18.51 Å2
Baniso -1Baniso -2Baniso -3
1-0.37 Å20 Å20 Å2
2---0.06 Å20 Å2
3----0.3 Å2
Refinement stepCycle: final / Resolution: 2→19.55 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2290 0 114 182 2586
Biso mean--43.78 41.56 -
Num. residues----290
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0192494
X-RAY DIFFRACTIONr_bond_other_d0.0010.022433
X-RAY DIFFRACTIONr_angle_refined_deg1.4911.9783346
X-RAY DIFFRACTIONr_angle_other_deg0.76235601
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9595298
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.72123.883103
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.80615445
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.321516
X-RAY DIFFRACTIONr_chiral_restr0.0870.2358
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0212999
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02551
LS refinement shellResolution: 2→2.052 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.268 85 -
Rwork0.243 1659 -
all-1744 -
obs--100 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
16.1514-0.54162.92611.5830.53255.96550.03750.04460.11310.0612-0.08870.0025-0.02440.00950.05120.0637-0.00130.03890.054-0.01070.0291-1.73539.095240.9819
22.85681.9076-1.10471.4082-0.79580.4987-0.0110.12460.0367-0.08340.01660.05950.0494-0.0667-0.00570.06680.0275-0.00620.0839-0.03950.026110.652545.110731.0383
31.58842.2072-0.57733.1479-0.8080.2202-0.34040.52710.515-0.35080.58640.89470.1339-0.2142-0.2460.7587-0.0033-0.10340.7397-0.12510.71877.008255.760714.5087
41.7782-0.29321.30822.937-1.25733.1695-0.05540.01180.1415-0.0923-0.0077-0.1042-0.17680.06970.06320.0216-0.00710.00530.0498-0.00970.017720.777257.536224.2878
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A118 - 178
2X-RAY DIFFRACTION2A179 - 275
3X-RAY DIFFRACTION3A276 - 316
4X-RAY DIFFRACTION4A317 - 420

+
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