[English] 日本語
Yorodumi
- PDB-7ovm: Protein kinase MKK7 in complex with cyclobutyl-substituted indazole -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ovm
TitleProtein kinase MKK7 in complex with cyclobutyl-substituted indazole
ComponentsDual specificity mitogen-activated protein kinase kinase 7
KeywordsTRANSFERASE / Inhibitor / Complex / MKK7 / Kinase / Triazole / Click-Chemistry / CuACC
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 / MAP kinase kinase activity / positive regulation of telomere maintenance / 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 / MAP kinase kinase activity / positive regulation of telomere maintenance / 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-21I / Dual specificity mitogen-activated protein kinase kinase 7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsBuehrmann, M. / Wiese, J.N. / Mueller, M.P. / Rauh, D.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Optimization of Covalent MKK7 Inhibitors via Crude Nanomole-Scale Libraries.
Authors: Gehrtz, P. / Marom, S. / Buhrmann, M. / Hardick, J. / Kleinbolting, S. / Shraga, A. / Dubiella, C. / Gabizon, R. / Wiese, J.N. / Muller, M.P. / Cohen, G. / Babaev, I. / Shurrush, K. / Avram, ...Authors: Gehrtz, P. / Marom, S. / Buhrmann, M. / Hardick, J. / Kleinbolting, S. / Shraga, A. / Dubiella, C. / Gabizon, R. / Wiese, J.N. / Muller, M.P. / Cohen, G. / Babaev, I. / Shurrush, K. / Avram, L. / Resnick, E. / Barr, H. / Rauh, D. / London, N.
History
DepositionJun 15, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 20, 2022Provider: repository / Type: Initial release
Revision 1.1Aug 17, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Nov 13, 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)36,5902
Polymers36,1471
Non-polymers4441
Water181
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area13310 Å2
Unit cell
Length a, b, c (Å)60.650, 68.900, 84.080
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#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: 36146.859 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 / Production host: Escherichia coli (E. coli)
References: UniProt: O14733, mitogen-activated protein kinase kinase
#2: Chemical ChemComp-21I / ~{N}-[(1-cyclobutyl-1,2,3-triazol-4-yl)methyl]-3-(1~{H}-indazol-3-yl)-5-(propanoylamino)benzamide


Mass: 443.501 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H25N7O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.43 Å3/Da / Density % sol: 49.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 180-220 mM sodium citrate, 15-25 % PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.9197 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Nov 20, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9197 Å / Relative weight: 1
ReflectionResolution: 2.9→50 Å / Num. obs: 8219 / % possible obs: 100 % / Redundancy: 13.14 % / Biso Wilson estimate: 83.37 Å2 / CC1/2: 0.99 / Rrim(I) all: 0.11 / Net I/σ(I): 17.65
Reflection shellResolution: 2.9→3 Å / Mean I/σ(I) obs: 2.18 / Num. unique obs: 763 / CC1/2: 0.81 / Rrim(I) all: 1.449

-
Processing

Software
NameVersionClassification
PHENIX1.19.1_4122refinement
PHENIX1.19.1_4122refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6QFL

6qfl


Resolution: 2.9→49.19 Å / SU ML: 0.591 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 33.7919
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2858 411 5 %
Rwork0.2298 7806 -
obs0.2326 8217 99.95 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 85.27 Å2
Refinement stepCycle: LAST / Resolution: 2.9→49.19 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2148 0 33 1 2182
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00222258
X-RAY DIFFRACTIONf_angle_d0.55753059
X-RAY DIFFRACTIONf_chiral_restr0.0409340
X-RAY DIFFRACTIONf_plane_restr0.0039393
X-RAY DIFFRACTIONf_dihedral_angle_d10.633827
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.9-3.320.43461330.31522535X-RAY DIFFRACTION99.96
3.32-4.180.29511360.24222578X-RAY DIFFRACTION100
4.18-49.190.25011420.2062693X-RAY DIFFRACTION99.93
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)
16.72034868318-1.42518325179-1.217879373197.6838989370.393630177943.228828274250.0660617160045-0.5385492258280.06252713203960.78464615729-0.2523969796341.075170138690.000641076743083-0.8620461003340.115247357630.66954577356-0.0573063146370.03191112915520.691507867925-0.09479133326720.685532977665-18.6772982019-15.216368046222.578607823
22.96684460331-0.193942409417-1.054647659073.92352396839-1.810848387495.11278635979-0.102316392796-0.08207360675050.0251559204957-0.0752129310883-0.0565093124047-0.2592546364050.1379637236450.4782318051910.1897594628910.4959722285050.0368017852675-0.03637574661030.609724026301-0.07549114562080.543959760764-8.02458581113-17.823274802917.4482107247
35.993213163682.42334731516-4.504527753148.34386273277-3.265826463499.005115744030.4221764639350.2136327389260.1891841717690.349612374426-0.1867702008150.352508873774-0.0662368245318-0.0290307996135-0.314838432990.687601782488-0.0079000852643-0.08983543480720.601991672895-0.03069287365940.546783269431-32.6182326993-0.3924137839430.41770170318
48.18303032199-4.150263687211.196444120611.66166915396-1.276801113681.88264908551-0.0380329245395-0.2994046545320.3200269790750.09734197261980.0489897255659-0.0987679566213-0.21167679806-0.04702370611770.004158776704170.673174653859-0.08242754233860.04384402473590.453025504526-0.02891566386410.649194696367-20.7882943189-5.9937538123411.2133518834
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 276 through 333 )276 - 333157 - 197
22chain 'A' and (resid 334 through 418 )334 - 418198 - 282
33chain 'A' and (resid 118 through 172 )118 - 1721 - 53
44chain 'A' and (resid 173 through 275 )173 - 27554 - 156

+
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