[English] 日本語
Yorodumi
- PDB-6nze: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN)... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6nze
TitleCRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5 AKA 4-[(2-CARBAMOYLPHEN YL)AMINO]-6-[(5-FLUOROPYRIDIN-2-YL)AMINO]-N-METHYLPYRIDINE -3-CARBOXAMIDE
ComponentsNon-receptor tyrosine-protein kinase TYK2
KeywordsTRANSFERASE / JTK1
Function / homology
Function and homology information


type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / interleukin-23-mediated signaling pathway / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / interleukin-12-mediated signaling pathway / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation ...type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / interleukin-23-mediated signaling pathway / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / interleukin-12-mediated signaling pathway / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of natural killer cell proliferation / growth hormone receptor binding / extrinsic component of plasma membrane / Other interleukin signaling / Interleukin-20 family signaling / type I interferon-mediated signaling pathway / Interleukin-6 signaling / MAPK3 (ERK1) activation / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of interleukin-17 production / Interleukin-10 signaling / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / type II interferon-mediated signaling pathway / Signaling by CSF3 (G-CSF) / positive regulation of T cell proliferation / non-specific protein-tyrosine kinase / positive regulation of receptor signaling pathway via JAK-STAT / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / cellular response to virus / Evasion by RSV of host interferon responses / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / cytoplasmic side of plasma membrane / positive regulation of type II interferon production / Interferon alpha/beta signaling / Signaling by ALK fusions and activated point mutants / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell differentiation / cytoskeleton / intracellular signal transduction / immune response / protein phosphorylation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / extracellular exosome / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Tyrosine-protein kinase, non-receptor, TYK2, N-terminal / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain ...Tyrosine-protein kinase, non-receptor, TYK2, N-terminal / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 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-L8Y / Non-receptor tyrosine-protein kinase TYK2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.96 Å
AuthorsMuckelbauer, J.M.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Identification ofN-Methyl Nicotinamide andN-Methyl Pyridazine-3-Carboxamide Pseudokinase Domain Ligands as Highly Selective Allosteric Inhibitors of Tyrosine Kinase 2 (TYK2).
Authors: Moslin, R. / Zhang, Y. / Wrobleski, S.T. / Lin, S. / Mertzman, M. / Spergel, S. / Tokarski, J.S. / Strnad, J. / Gillooly, K. / McIntyre, K.W. / Zupa-Fernandez, A. / Cheng, L. / Sun, H. / ...Authors: Moslin, R. / Zhang, Y. / Wrobleski, S.T. / Lin, S. / Mertzman, M. / Spergel, S. / Tokarski, J.S. / Strnad, J. / Gillooly, K. / McIntyre, K.W. / Zupa-Fernandez, A. / Cheng, L. / Sun, H. / Chaudhry, C. / Huang, C. / D'Arienzo, C. / Heimrich, E. / Yang, X. / Muckelbauer, J.K. / Chang, C. / Tredup, J. / Mulligan, D. / Xie, D. / Aranibar, N. / Chiney, M. / Burke, J.R. / Lombardo, L. / Carter, P.H. / Weinstein, D.S.
History
DepositionFeb 13, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 24, 2019Provider: repository / Type: Initial release
Revision 1.1Nov 6, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Oct 11, 2023Group: 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 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Non-receptor tyrosine-protein kinase TYK2
B: Non-receptor tyrosine-protein kinase TYK2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,1438
Polymers70,9982
Non-polymers1,1456
Water2,738152
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1630 Å2
ΔGint-48 kcal/mol
Surface area21200 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.590, 65.360, 74.540
Angle α, β, γ (deg.)90.000, 112.170, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Non-receptor tyrosine-protein kinase TYK2


Mass: 35499.156 Da / Num. of mol.: 2 / Fragment: Pseudo kinase domain, residues 575-869
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TYK2 / Plasmid: pFastBac1 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF9
References: UniProt: P29597, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-L8Y / 4-[(2-carbamoylphenyl)amino]-6-[(5-fluoropyridin-2-yl)amino]-N-methylpyridine-3-carboxamide


Mass: 380.376 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H17FN6O2
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 152 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.37 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 200 mM ammonium sulfate, and 100 mM HEPES buffer, pH 7.5, 30%(W/V) PEG 5000 (Methyl Ether)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 16, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.96→47.46 Å / Num. obs: 43047 / % possible obs: 96.8 % / Redundancy: 3.3 % / Net I/σ(I): 11.9
Reflection shellResolution: 1.96→2.07 Å

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
PDB_EXTRACT3.24data extraction
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4WOV

4wov


Resolution: 1.96→47.46 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.921 / Rfactor Rfree error: 0.01 / SU R Cruickshank DPI: 0.216 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.146 / SU Rfree Blow DPI: 0.134 / SU Rfree Cruickshank DPI: 0.136
RfactorNum. reflection% reflectionSelection details
Rfree0.227 2172 5.05 %RANDOM
Rwork0.196 ---
obs0.197 43019 96.3 %-
Displacement parametersBiso max: 119.33 Å2 / Biso mean: 34.24 Å2 / Biso min: 18.34 Å2
Baniso -1Baniso -2Baniso -3
1-5.9305 Å20 Å21.9742 Å2
2---6.7421 Å20 Å2
3---0.8116 Å2
Refine analyzeLuzzati coordinate error obs: 0.24 Å
Refinement stepCycle: final / Resolution: 1.96→47.46 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3735 0 76 152 3963
Biso mean--38.83 39.05 -
Num. residues----504
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1549SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes59HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1238HARMONIC5
X-RAY DIFFRACTIONt_it7499HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion513SEMIHARMONIC5
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_contact8095SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d7499HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg13520HARMONIC21.05
X-RAY DIFFRACTIONt_omega_torsion3.72
X-RAY DIFFRACTIONt_other_torsion14.18
LS refinement shellResolution: 1.96→2.01 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.231 153 4.91 %
Rwork0.197 2961 -
all0.199 3114 -
obs--95.16 %

+
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