[English] 日本語
Yorodumi
- PDB-3krr: Crystal Structure of JAK2 complexed with a potent quinoxaline ATP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3krr
TitleCrystal Structure of JAK2 complexed with a potent quinoxaline ATP site inhibitor
ComponentsTyrosine-protein kinase JAK2
KeywordsTRANSFERASE / Small molecule inhibitor / ATP site kinase inhibitor / ATP-binding / Disease mutation / Kinase / Membrane / Nucleotide-binding / Phosphoprotein / Proto-oncogene / SH2 domain / Tyrosine-protein kinase
Function / homology
Function and homology information


interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic 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 / Signaling by Erythropoietin ...interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic 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 / Signaling by Erythropoietin / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / interleukin-12 receptor binding / post-embryonic hemopoiesis / collagen-activated signaling pathway / Erythropoietin activates STAT5 / Erythropoietin activates Phospholipase C gamma (PLCG) / interleukin-5-mediated signaling pathway / response to interleukin-12 / positive regulation of leukocyte proliferation / activation of Janus kinase activity / interleukin-12 receptor complex / interleukin-23 receptor complex / positive regulation of platelet aggregation / tyrosine phosphorylation of STAT protein / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / positive regulation of platelet activation / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / interleukin-3-mediated signaling pathway / regulation of nitric oxide biosynthetic process / acetylcholine receptor binding / cellular response to interleukin-3 / Signaling by Leptin / positive regulation of signaling receptor activity / Interleukin-12 signaling / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / positive regulation of cell-substrate adhesion / response to hydroperoxide / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / negative regulation of cardiac muscle cell apoptotic process / positive regulation of epithelial cell apoptotic process / axon regeneration / peptide hormone receptor binding / growth hormone receptor signaling pathway / intrinsic apoptotic signaling pathway in response to oxidative stress / IFNG signaling activates MAPKs / extrinsic component of plasma membrane / Interleukin-20 family signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin-6 signaling / enzyme-linked receptor protein signaling pathway / interleukin-6-mediated signaling pathway / negative regulation of cell-cell adhesion / Prolactin receptor signaling / positive regulation of interleukin-17 production / negative regulation of DNA binding / MAPK3 (ERK1) activation / response to amine / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / positive regulation of natural killer cell proliferation / mesoderm development / positive regulation of SMAD protein signal transduction / cell surface receptor signaling pathway via JAK-STAT / platelet-derived growth factor receptor signaling pathway / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / growth hormone receptor signaling pathway via JAK-STAT / response to tumor necrosis factor / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / Erythropoietin activates RAS / Growth hormone receptor signaling / positive regulation of apoptotic signaling pathway / extrinsic apoptotic signaling pathway / Signaling by CSF3 (G-CSF) / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of T cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / extrinsic component of cytoplasmic side of plasma membrane / SH2 domain binding / cellular response to dexamethasone stimulus / post-translational protein modification / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / caveola / endosome lumen / positive regulation of cell differentiation
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 / Jak1 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 / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / SH2 domain / 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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-DQX / Tyrosine-protein kinase JAK2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.8 Å
AuthorsTavares, G.A. / Gerspacher, M. / Kroemer, M. / Scheufler, C.
CitationJournal: Mol.Cancer Ther. / Year: 2010
Title: Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805
Authors: Baffert, F. / Regnier, C.H. / De Pover, A. / Pissot-Soldermann, C. / Tavares, G.A. / Blasco, F. / Brueggen, J. / Chene, P. / Drueckes, P. / Erdmann, D. / Furet, P. / Gerspacher, M. / Lang, M. ...Authors: Baffert, F. / Regnier, C.H. / De Pover, A. / Pissot-Soldermann, C. / Tavares, G.A. / Blasco, F. / Brueggen, J. / Chene, P. / Drueckes, P. / Erdmann, D. / Furet, P. / Gerspacher, M. / Lang, M. / Ledieu, D. / Nolan, L. / Ruetz, S. / Trappe, J. / Vangrevelinghe, E. / Wartmann, M. / Wyder, L. / Hofmann, F. / Radimerski, T.
History
DepositionNov 19, 2009Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jul 21, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance

-
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)35,2132
Polymers34,7221
Non-polymers4911
Water3,441191
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)93.312, 103.009, 68.739
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Tyrosine-protein kinase JAK2 / Janus kinase 2 / JAK-2


Mass: 34722.484 Da / Num. of mol.: 1 / Fragment: kinase domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: PACG2TTEV / Cell line (production host): SF9DE / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O60674, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-DQX / 8-[3,5-difluoro-4-(morpholin-4-ylmethyl)phenyl]-2-(1-piperidin-4-yl-1H-pyrazol-4-yl)quinoxaline


Mass: 490.548 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H28F2N6O
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 191 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.29 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 1.2M NA CITRATE, 0.1M HEPES, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.97812 / Wavelength: 0.97812 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Feb 22, 2008 / Details: Sagitally Focused SI(III)
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97812 Å / Relative weight: 1
ReflectionResolution: 1.8→60 Å / Num. obs: 31069 / % possible obs: 100 % / Redundancy: 7.2 % / Rmerge(I) obs: 0.078 / Net I/σ(I): 16.15
Reflection shellResolution: 1.8→1.88 Å / Redundancy: 6.57 % / Rmerge(I) obs: 0.483 / Mean I/σ(I) obs: 4.02 / % possible all: 100

-
Processing

Software
NameVersionClassification
CCP4model building
REFMAC5.5.0063refinement
XDSdata reduction
XSCALEdata scaling
CCP4phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.8→50 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.939 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 2.237 / SU ML: 0.07 / Cross valid method: THROUGHOUT / ESU R: 0.113 / ESU R Free: 0.112 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES WERE REFINED INDIVIDUALLY.
RfactorNum. reflection% reflectionSelection details
Rfree0.20587 1554 5 %RANDOM
Rwork0.16699 ---
obs0.16893 29513 99.99 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 59.15 Å2 / Biso mean: 18.974 Å2 / Biso min: 11.45 Å2
Baniso -1Baniso -2Baniso -3
1--0.9 Å20 Å20 Å2
2--1.21 Å20 Å2
3----0.31 Å2
Refinement stepCycle: LAST / Resolution: 1.8→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2382 0 36 191 2609
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0222484
X-RAY DIFFRACTIONr_bond_other_d0.0010.021701
X-RAY DIFFRACTIONr_angle_refined_deg1.1711.9883360
X-RAY DIFFRACTIONr_angle_other_deg0.83934134
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4845294
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.09924.016122
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.36115443
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.3771518
X-RAY DIFFRACTIONr_chiral_restr0.0720.2352
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212726
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02498
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.17321463
X-RAY DIFFRACTIONr_mcbond_other0.3042590
X-RAY DIFFRACTIONr_mcangle_it2.1932367
X-RAY DIFFRACTIONr_scbond_it3.2864.51021
X-RAY DIFFRACTIONr_scangle_it5.2886992
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.8→1.847 Å / Rfactor Rfree error: 0.112 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.256 115 -
Rwork0.228 2173 -
all-2288 -
obs--100 %

+
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