[English] 日本語
Yorodumi
- PDB-8b9e: Crystal structure of JAK2 JH2-V617F in complex with Z902-A3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8b9e
TitleCrystal structure of JAK2 JH2-V617F in complex with Z902-A3
ComponentsTyrosine-protein kinase JAK2
KeywordsTRANSFERASE / Janus kinase / pseudokinase / inhibitor complex / JAK2 / JH2
Function / homology
Function and homology information


interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / thrombopoietin-mediated signaling pathway / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway ...interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / thrombopoietin-mediated signaling pathway / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / Signaling by Erythropoietin / collagen-activated signaling pathway / interleukin-12 receptor binding / Erythropoietin activates STAT5 / interleukin-5-mediated signaling pathway / activation of Janus kinase activity / response to interleukin-12 / Erythropoietin activates Phospholipase C gamma (PLCG) / positive regulation of leukocyte proliferation / post-embryonic hemopoiesis / interleukin-12 receptor complex / erythropoietin-mediated signaling pathway / interleukin-23 receptor complex / interleukin-23-mediated signaling pathway / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / 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 / acetylcholine receptor binding / positive regulation of platelet activation / regulation of nitric oxide biosynthetic process / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / positive regulation of platelet aggregation / Signaling by Leptin / Interleukin-12 signaling / positive regulation of epithelial cell apoptotic process / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / regulation of receptor signaling pathway via JAK-STAT / positive regulation of natural killer cell proliferation / growth hormone receptor binding / positive regulation of cell-substrate adhesion / growth hormone receptor signaling pathway / axon regeneration / extrinsic component of cytoplasmic side of plasma membrane / response to hydroperoxide / negative regulation of cardiac muscle cell apoptotic process / positive regulation of tyrosine phosphorylation of STAT protein / intrinsic apoptotic signaling pathway in response to oxidative stress / extrinsic component of plasma membrane / negative regulation of cell-cell adhesion / peptide hormone receptor binding / Interleukin-20 family signaling / IFNG signaling activates MAPKs / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / enzyme-linked receptor protein signaling pathway / MAPK3 (ERK1) activation / Prolactin receptor signaling / : / response to amine / signaling receptor activator activity / mesoderm development / MAPK1 (ERK2) activation / positive regulation of interleukin-17 production / platelet-derived growth factor receptor signaling pathway / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / response to tumor necrosis factor / positive regulation of SMAD protein signal transduction / growth hormone receptor signaling pathway via JAK-STAT / cell surface receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / Growth hormone receptor signaling / Erythropoietin activates RAS / positive regulation of T cell proliferation / Signaling by CSF3 (G-CSF) / tumor necrosis factor-mediated signaling pathway / extrinsic apoptotic signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / post-translational protein modification / lipopolysaccharide-mediated signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / erythrocyte differentiation / positive regulation of interleukin-1 beta production / endosome lumen / positive regulation of cell differentiation / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of apoptotic signaling pathway
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / 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 / : ...Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / 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 central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Src homology 2 (SH2) domain profile. / 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. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-Q7F / Tyrosine-protein kinase JAK2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsHaikarainen, T. / Silvennoinen, O.
Funding support Finland, 1items
OrganizationGrant numberCountry
Academy of Finland Finland
CitationJournal: Pharmaceuticals / Year: 2023
Title: Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain.
Authors: Virtanen, A.T. / Haikarainen, T. / Sampathkumar, P. / Palmroth, M. / Liukkonen, S. / Liu, J. / Nekhotiaeva, N. / Hubbard, S.R. / Silvennoinen, O.
History
DepositionOct 5, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 1, 2023Provider: repository / Type: Initial release
Revision 1.1Feb 7, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Oct 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: Tyrosine-protein kinase JAK2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,8094
Polymers33,2841
Non-polymers5253
Water6,251347
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area310 Å2
ΔGint-1 kcal/mol
Surface area13490 Å2
Unit cell
Length a, b, c (Å)53.466, 56.555, 114.932
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 Tyrosine-protein kinase JAK2 / Janus kinase 2 / JAK-2


Mass: 33284.133 Da / Num. of mol.: 1 / Mutation: W777A, F794H, V617F
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O60674, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-Q7F / 6-[[methyl-[(3-methylthiophen-2-yl)methyl]amino]methyl]-~{N}4-phenyl-1,3,5-triazine-2,4-diamine


Mass: 340.446 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H20N6S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 347 / 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: 2.61 Å3/Da / Density % sol: 52.88 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.1M Tris pH 8, 20% PEG4000, 0.2M Na-acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Jul 3, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 1.5→57.466 Å / Num. obs: 98889 / % possible obs: 91.6 % / Redundancy: 6.1 % / Biso Wilson estimate: 22.61 Å2 / CC1/2: 0.999 / Net I/σ(I): 13.68
Reflection shellResolution: 1.5→1.59 Å / Redundancy: 3.4 % / Mean I/σ(I) obs: 0.77 / Num. unique obs: 10775 / CC1/2: 0.915 / % possible all: 61.5

-
Processing

Software
NameVersionClassification
GDAdata collection
PHENIX1.19.2_4158refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4fvr

4fvr


Resolution: 1.5→40.31 Å / SU ML: 0.1993 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 23.6009
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1938 4955 5.01 %
Rwork0.1689 93913 -
obs0.1702 98868 91.56 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 31.55 Å2
Refinement stepCycle: LAST / Resolution: 1.5→40.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2194 0 36 347 2577
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01662357
X-RAY DIFFRACTIONf_angle_d1.26783209
X-RAY DIFFRACTIONf_chiral_restr0.1063350
X-RAY DIFFRACTIONf_plane_restr0.0121417
X-RAY DIFFRACTIONf_dihedral_angle_d16.7566893
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.5-1.520.391990.3711786X-RAY DIFFRACTION51.99
1.52-1.530.38091040.37421923X-RAY DIFFRACTION56.09
1.53-1.550.39951100.3362104X-RAY DIFFRACTION62.47
1.55-1.570.33851230.31652298X-RAY DIFFRACTION66.02
1.57-1.590.36021270.30662471X-RAY DIFFRACTION73.37
1.59-1.620.29881430.29152683X-RAY DIFFRACTION76.5
1.62-1.640.29641480.27462776X-RAY DIFFRACTION83.42
1.64-1.660.27431620.273097X-RAY DIFFRACTION88.9
1.66-1.690.31291650.27453184X-RAY DIFFRACTION94.26
1.69-1.720.30221800.2623336X-RAY DIFFRACTION97.64
1.72-1.750.26361740.23013326X-RAY DIFFRACTION98.26
1.75-1.780.21411840.20963462X-RAY DIFFRACTION99.54
1.78-1.810.24951790.19613398X-RAY DIFFRACTION100
1.81-1.850.22911780.18683429X-RAY DIFFRACTION100
1.85-1.890.25521790.18723418X-RAY DIFFRACTION99.86
1.89-1.930.22191810.18223374X-RAY DIFFRACTION99.94
1.93-1.980.19731800.18273462X-RAY DIFFRACTION100
1.98-2.040.21671770.17923387X-RAY DIFFRACTION100
2.04-2.090.18391780.17063434X-RAY DIFFRACTION99.97
2.1-2.160.21041760.15683431X-RAY DIFFRACTION100
2.16-2.240.18031770.15043408X-RAY DIFFRACTION99.92
2.24-2.330.16871820.15843429X-RAY DIFFRACTION99.97
2.33-2.440.17931830.15943413X-RAY DIFFRACTION100
2.44-2.560.18741760.15423397X-RAY DIFFRACTION100
2.56-2.720.21221840.15883410X-RAY DIFFRACTION99.94
2.72-2.930.20321820.1623423X-RAY DIFFRACTION99.89
2.93-3.230.17591770.15723413X-RAY DIFFRACTION99.97
3.23-3.70.1961840.14863401X-RAY DIFFRACTION99.92
3.7-4.660.12961840.13133421X-RAY DIFFRACTION100
4.66-40.310.16271790.16333419X-RAY DIFFRACTION99.78

+
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