[English] 日本語
Yorodumi
- PDB-7q6h: HUMAN JAK3 KINASE DOMAIN WITH 1-(4-((2-((1-methyl-1H-pyrazol-4-yl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7q6h
TitleHUMAN JAK3 KINASE DOMAIN WITH 1-(4-((2-((1-methyl-1H-pyrazol-4-yl)amino)quinazolin-8-yl)amino)piperidin-1-yl)ethan-1-one
ComponentsTyrosine-protein kinase JAK3
KeywordsSIGNALING PROTEIN / INHIBITOR / JAK3 / KINASE
Function / homology
Function and homology information


negative regulation of dendritic cell cytokine production / negative regulation of FasL production / response to interleukin-9 / response to interleukin-2 / response to interleukin-15 / response to interleukin-4 / negative regulation of T-helper 1 cell differentiation / tyrosine phosphorylation of STAT protein / negative regulation of T-helper 17 cell lineage commitment / Interleukin-9 signaling ...negative regulation of dendritic cell cytokine production / negative regulation of FasL production / response to interleukin-9 / response to interleukin-2 / response to interleukin-15 / response to interleukin-4 / negative regulation of T-helper 1 cell differentiation / tyrosine phosphorylation of STAT protein / negative regulation of T-helper 17 cell lineage commitment / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-7-mediated signaling pathway / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / negative regulation of T cell activation / interleukin-2-mediated signaling pathway / regulation of T cell apoptotic process / negative regulation of interleukin-12 production / interleukin-15-mediated signaling pathway / negative regulation of thymocyte apoptotic process / Interleukin-15 signaling / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / Interleukin-2 signaling / extrinsic component of cytoplasmic side of plasma membrane / extrinsic component of plasma membrane / Signaling by ALK / Interleukin-20 family signaling / negative regulation of interleukin-10 production / enzyme-linked receptor protein signaling pathway / T cell homeostasis / growth hormone receptor signaling pathway via JAK-STAT / cell surface receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / Interleukin-7 signaling / B cell differentiation / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cytokine-mediated signaling pathway / cytoplasmic side of plasma membrane / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / regulation of apoptotic process / Interleukin-4 and Interleukin-13 signaling / adaptive immune response / Potential therapeutics for SARS / cell differentiation / cytoskeleton / intracellular signal transduction / endosome / innate immune response / ATP binding / plasma membrane / cytosol
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak3 / 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 Jak3 / 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 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. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-934 / 1-phenylurea / Tyrosine-protein kinase JAK3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.749 Å
AuthorsChung, C.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: J.Med.Chem. / Year: 2022
Title: Investigation of Janus Kinase (JAK) Inhibitors for Lung Delivery and the Importance of Aldehyde Oxidase Metabolism.
Authors: Wellaway, C.R. / Baldwin, I.R. / Bamborough, P. / Barker, D. / Bartholomew, M.A. / Chung, C.W. / Dumpelfeld, B. / Evans, J.P. / Fazakerley, N.J. / Homes, P. / Keeling, S.P. / Lewell, X.Q. / ...Authors: Wellaway, C.R. / Baldwin, I.R. / Bamborough, P. / Barker, D. / Bartholomew, M.A. / Chung, C.W. / Dumpelfeld, B. / Evans, J.P. / Fazakerley, N.J. / Homes, P. / Keeling, S.P. / Lewell, X.Q. / McNab, F.W. / Morley, J. / Needham, D. / Neu, M. / van Oosterhout, A.J.M. / Pal, A. / Reinhard, F.B.M. / Rianjongdee, F. / Robertson, C.M. / Rowland, P. / Shah, R.R. / Sherriff, E.B. / Sloan, L.A. / Teague, S. / Thomas, D.A. / Wellaway, N. / Wojno-Picon, J. / Woolven, J.M. / Coe, D.M.
History
DepositionNov 7, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 2, 2022Provider: repository / Type: Initial release
Revision 1.1May 1, 2024Group: Data collection / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
AAA: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,7754
Polymers37,1771
Non-polymers5983
Water6,720373
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area200 Å2
ΔGint-13 kcal/mol
Surface area13720 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.120, 75.244, 89.449
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Tyrosine-protein kinase JAK3 / Janus kinase 3 / JAK-3 / Leukocyte janus kinase / L-JAK


Mass: 37177.340 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK3 / Production host: Escherichia coli BL21 (bacteria)
References: UniProt: P52333, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-934 / 1-[4-[[2-[(1-methylpyrazol-4-yl)amino]quinazolin-8-yl]amino]piperidin-1-yl]ethanone / 1-(4-((2-((1-methyl-1H-pyrazol-4-yl)amino)quinazolin-8-yl)amino)piperidin-1-yl)ethan-1-one


Mass: 365.432 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H23N7O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-PHU / 1-phenylurea / Phenylurea


Mass: 136.151 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C7H8N2O
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 373 / 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

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.32 %
Crystal growTemperature: 293 K / Method: vapor diffusion
Details: 8-20% PEG3350 and 0.2-0.3M ammonium sulphate (AS). 2% phenylurea

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.984 Å
DetectorType: DECTRIS EIGER X 4M / Detector: PIXEL / Date: May 13, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.984 Å / Relative weight: 1
ReflectionResolution: 1.749→89.45 Å / Num. obs: 32901 / % possible obs: 99.9 % / Redundancy: 6.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.065 / Net I/σ(I): 15.3
Reflection shellResolution: 1.75→1.87 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.605 / Mean I/σ(I) obs: 2.6 / Num. unique obs: 5836 / CC1/2: 0.848 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: in house

Resolution: 1.749→57.581 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.938 / SU B: 2.547 / SU ML: 0.08 / Cross valid method: FREE R-VALUE / ESU R: 0.121 / ESU R Free: 0.117
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2202 1593 4.851 %
Rwork0.1827 31248 -
all0.185 --
obs-32841 99.924 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK
Displacement parametersBiso mean: 32.526 Å2
Baniso -1Baniso -2Baniso -3
1-1.246 Å20 Å2-0 Å2
2---0.881 Å2-0 Å2
3----0.365 Å2
Refinement stepCycle: LAST / Resolution: 1.749→57.581 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2259 0 42 373 2674
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0132485
X-RAY DIFFRACTIONr_bond_other_d0.0040.0172348
X-RAY DIFFRACTIONr_angle_refined_deg1.1611.6423389
X-RAY DIFFRACTIONr_angle_other_deg1.2311.5915427
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8055315
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.89620.423142
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.62115429
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.3231525
X-RAY DIFFRACTIONr_chiral_restr0.0570.2299
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022838
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02613
X-RAY DIFFRACTIONr_nbd_refined0.1950.2463
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1760.22129
X-RAY DIFFRACTIONr_nbtor_refined0.1610.21173
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0760.21032
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1610.2282
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0580.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1630.218
X-RAY DIFFRACTIONr_nbd_other0.1730.272
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1660.232
X-RAY DIFFRACTIONr_mcbond_it2.1514.0951177
X-RAY DIFFRACTIONr_mcbond_other2.154.0911176
X-RAY DIFFRACTIONr_mcangle_it3.2059.191483
X-RAY DIFFRACTIONr_mcangle_other3.2049.1981484
X-RAY DIFFRACTIONr_scbond_it3.0124.6711308
X-RAY DIFFRACTIONr_scbond_other3.0114.671309
X-RAY DIFFRACTIONr_scangle_it4.73110.221893
X-RAY DIFFRACTIONr_scangle_other4.72910.2191894
X-RAY DIFFRACTIONr_lrange_it6.60538.5032952
X-RAY DIFFRACTIONr_lrange_other6.60438.4962953
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
1.749-1.7940.2551210.2522470.2523760.8820.88699.66330.244
1.794-1.8430.2941080.23722030.2423120.8460.87499.95670.227
1.843-1.8970.2751070.23721640.23922720.8670.88799.9560.225
1.897-1.9550.265950.21821010.2221980.8870.91399.9090.206
1.955-2.0190.2281090.20420480.20521580.9230.9499.95370.193
2.019-2.090.22920.20219740.20320680.940.93899.90330.188
2.09-2.1680.199880.19419280.19420190.9490.9599.85140.181
2.168-2.2570.2930.1718280.17119210.9510.961000.158
2.257-2.3570.199920.16817810.16918730.9510.9561000.155
2.357-2.4720.205900.17516790.17617690.9490.9541000.163
2.472-2.6050.236650.16116350.16417000.9430.9581000.153
2.605-2.7630.194860.16415080.16615970.9510.96199.81210.156
2.763-2.9530.222780.17514490.17715270.9470.9551000.169
2.953-3.1890.248600.17913530.18114130.9220.9531000.177
3.189-3.4920.206590.17912560.1813160.9510.96399.9240.181
3.492-3.9030.182640.16611370.16712010.960.9651000.174
3.903-4.5030.201700.1569920.15910630.9650.97299.90590.173
4.503-5.5070.215490.1778560.1799050.9630.9631000.196
5.507-7.7530.296450.2116890.2157350.8960.9499.86390.233
7.753-57.5810.271220.2084200.2114430.9150.94799.77430.257

+
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