[English] 日本語
Yorodumi
- PDB-8deg: Crystal structure of DLK in complex with inhibitor DN0011197 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8deg
TitleCrystal structure of DLK in complex with inhibitor DN0011197
ComponentsMitogen-activated protein kinase kinase kinase 12
KeywordsSIGNALING PROTEIN / TRANSFERASE/INHIBITOR / DLK / kinase / inhibitor / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


mitogen-activated protein kinase kinase kinase / JUN kinase kinase kinase activity / negative regulation of motor neuron apoptotic process / positive regulation of protein kinase activity / positive regulation of JUN kinase activity / JNK cascade / post-translational protein modification / protein serine/threonine kinase activator activity / growth cone / peptidyl-serine phosphorylation ...mitogen-activated protein kinase kinase kinase / JUN kinase kinase kinase activity / negative regulation of motor neuron apoptotic process / positive regulation of protein kinase activity / positive regulation of JUN kinase activity / JNK cascade / post-translational protein modification / protein serine/threonine kinase activator activity / growth cone / peptidyl-serine phosphorylation / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / protein kinase activity / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / protein kinase binding / positive regulation of DNA-templated transcription / protein homodimerization activity / ATP binding / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Mitogen-activated protein kinase kinase kinase 12/13 / Mitogen-activated protein kinase kinase kinase 12 / : / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-SIQ / Mitogen-activated protein kinase kinase kinase 12
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.79 Å
AuthorsSrivastava, A. / Lexa, K. / de Vicente, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors with Neuroprotective Properties in In Vitro and In Vivo Models of Amyotrophic Lateral Sclerosis.
Authors: Craig 2nd, R.A. / Fox, B.M. / Hu, C. / Lexa, K.W. / Osipov, M. / Thottumkara, A.P. / Larhammar, M. / Miyamoto, T. / Rana, A. / Kane, L.A. / Yulyaningsih, E. / Solanoy, H. / Nguyen, H. / ...Authors: Craig 2nd, R.A. / Fox, B.M. / Hu, C. / Lexa, K.W. / Osipov, M. / Thottumkara, A.P. / Larhammar, M. / Miyamoto, T. / Rana, A. / Kane, L.A. / Yulyaningsih, E. / Solanoy, H. / Nguyen, H. / Chau, R. / Earr, T. / Kajiwara, Y. / Fleck, D. / Lucas, A. / Haddick, P.C.G. / Takahashi, R.H. / Tong, V. / Wang, J. / Canet, M.J. / Poda, S.B. / Scearce-Levie, K. / Srivastava, A. / Sweeney, Z.K. / Xu, M. / Zhang, R. / He, J. / Lei, Y. / Zhuo, Z. / de Vicente, J.
History
DepositionJun 20, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 14, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 4, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase kinase kinase 12
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,8832
Polymers36,4101
Non-polymers4731
Water54030
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)57.837, 39.141, 62.781
Angle α, β, γ (deg.)90.000, 106.990, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Mitogen-activated protein kinase kinase kinase 12 / Dual leucine zipper bearing kinase / DLK / Leucine-zipper protein kinase / ZPK / MAPK-upstream ...Dual leucine zipper bearing kinase / DLK / Leucine-zipper protein kinase / ZPK / MAPK-upstream kinase / MUK / Mixed lineage kinase


Mass: 36409.797 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K12, ZPK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q12852, mitogen-activated protein kinase kinase kinase
#2: Chemical ChemComp-SIQ / methyl (1S,4S)-5-{(4P)-4-[5-amino-6-(difluoromethoxy)pyrazin-2-yl]-6-[(1R,4R)-2-azabicyclo[2.1.1]hexan-2-yl]pyridin-2-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate


Mass: 473.476 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H25F2N7O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 30 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 7.7
Details: 0.2M Magnesium Acetate, 0.1M HEPES pH 7.7, 18% PEG 3350

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.97853 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 25, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97853 Å / Relative weight: 1
ReflectionResolution: 2.79→30.43 Å / Num. obs: 6597 / % possible obs: 96.3 % / Redundancy: 3.1 % / Rmerge(I) obs: 0.121 / Net I/σ(I): 8.9
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.399 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 539 / % possible all: 81.2

-
Processing

Software
NameVersionClassification
REFMAC5.8.0238refinement
PDB_EXTRACT3.27data extraction
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: Not public

Resolution: 2.79→30.43 Å / Cor.coef. Fo:Fc: 0.903 / Cor.coef. Fo:Fc free: 0.843 / SU B: 24.615 / SU ML: 0.44 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.508 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2966 336 5.1 %RANDOM
Rwork0.2484 ---
obs0.2508 6249 95.68 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 102.67 Å2 / Biso mean: 50.248 Å2 / Biso min: 22.48 Å2
Baniso -1Baniso -2Baniso -3
1-0.46 Å2-0 Å2-1.22 Å2
2---2.03 Å2-0 Å2
3---1.95 Å2
Refinement stepCycle: final / Resolution: 2.79→30.43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2140 0 34 30 2204
Biso mean--40.74 31.82 -
Num. residues----267
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0020.0132236
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172097
X-RAY DIFFRACTIONr_angle_refined_deg1.2251.6563040
X-RAY DIFFRACTIONr_angle_other_deg1.0281.5914871
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.3375265
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.94322.243107
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.96715383
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.9631512
X-RAY DIFFRACTIONr_chiral_restr0.0360.2281
X-RAY DIFFRACTIONr_gen_planes_refined0.0020.022427
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02464
LS refinement shellResolution: 2.792→2.864 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.338 20 -
Rwork0.377 338 -
all-358 -
obs--71.74 %

+
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