[English] 日本語
Yorodumi
- PDB-4hvh: JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4hvh
TitleJAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl
ComponentsTyrosine-protein kinase JAK3
KeywordsTransferase/Transferase Inhibitor / Kinase-Inhibitor Complex / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


negative regulation of dendritic cell cytokine 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 / : / 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-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / cytokine-mediated signaling pathway / cytoplasmic side of plasma membrane / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / Interleukin-4 and Interleukin-13 signaling / regulation of apoptotic process / histone H3Y41 kinase activity / histone H2AXY142 kinase activity / 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 / 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-19R / Tyrosine-protein kinase JAK3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.3 Å
AuthorsKuglstatter, A. / Shao, A.
CitationJournal: J.Med.Chem. / Year: 2013
Title: 3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models.
Authors: Soth, M. / Hermann, J.C. / Yee, C. / Alam, M. / Barnett, J.W. / Berry, P. / Browner, M.F. / Frank, K. / Frauchiger, S. / Harris, S. / He, Y. / Hekmat-Nejad, M. / Hendricks, T. / Henningsen, ...Authors: Soth, M. / Hermann, J.C. / Yee, C. / Alam, M. / Barnett, J.W. / Berry, P. / Browner, M.F. / Frank, K. / Frauchiger, S. / Harris, S. / He, Y. / Hekmat-Nejad, M. / Hendricks, T. / Henningsen, R. / Hilgenkamp, R. / Ho, H. / Hoffman, A. / Hsu, P.Y. / Hu, D.Q. / Itano, A. / Jaime-Figueroa, S. / Jahangir, A. / Jin, S. / Kuglstatter, A. / Kutach, A.K. / Liao, C. / Lynch, S. / Menke, J. / Niu, L. / Patel, V. / Railkar, A. / Roy, D. / Shao, A. / Shaw, D. / Steiner, S. / Sun, Y. / Tan, S.L. / Wang, S. / Vu, M.D.
History
DepositionNov 6, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 16, 2013Provider: repository / Type: Initial release
Revision 1.1Jan 30, 2013Group: Database references
Revision 1.2Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,9022
Polymers35,6141
Non-polymers2881
Water1,26170
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)46.749, 75.540, 89.217
Angle α, β, γ (deg.)90.00, 90.00, 90.00
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: 35613.598 Da / Num. of mol.: 1 / Fragment: RESIDUES 811-1124 / Mutation: C1040S, C1048S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK3 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P52333, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-19R / 2-cyclopropyl-N-[(2R)-3-hydroxy-3-methylbutan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide


Mass: 288.345 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H20N4O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 70 / 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: 2.21 Å3/Da / Density % sol: 44.39 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 30% PEG3350, 0.1M MES, 0.2M MgCl, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.97946 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.3→44.59 Å / Num. obs: 12593 / % possible obs: 90.7 % / Redundancy: 4.5 % / Biso Wilson estimate: 37.2 Å2 / Rsym value: 0.091 / Net I/σ(I): 13.4
Reflection shellResolution: 2.3→2.36 Å / Redundancy: 2.7 % / Mean I/σ(I) obs: 1.7 / Num. unique all: 763 / Rsym value: 0.49 / % possible all: 72.3

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB entry 4HVD

4hvd


Resolution: 2.3→36.31 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.893 / SU B: 18.068 / SU ML: 0.2 / Cross valid method: THROUGHOUT / ESU R: 0.461 / ESU R Free: 0.294 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.28289 658 5 %RANDOM
Rwork0.22734 ---
obs0.23004 12593 90.7 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 43.673 Å2
Baniso -1Baniso -2Baniso -3
1-3.19 Å20 Å20 Å2
2---0.95 Å20 Å2
3----2.24 Å2
Refinement stepCycle: LAST / Resolution: 2.3→36.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2228 0 21 70 2319
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0222308
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.0611.9933126
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.1965275
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.58522.804107
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.9815393
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.111521
X-RAY DIFFRACTIONr_chiral_restr0.0750.2332
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.021773
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.1940.2989
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3020.21570
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.150.2103
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1580.232
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1990.24
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.6351.51432
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.10922237
X-RAY DIFFRACTIONr_scbond_it1.37331000
X-RAY DIFFRACTIONr_scangle_it2.2264.5886
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.3→2.36 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.354 41 -
Rwork0.275 725 -
obs--72.33 %
Refinement TLS params.Method: refined / Origin x: 3.0969 Å / Origin y: -13.6901 Å / Origin z: -14.6393 Å
111213212223313233
T-0.036 Å20.002 Å20.0065 Å2--0.0379 Å20.0226 Å2---0.0067 Å2
L0.3459 °2-0.001 °2-0.1432 °2-0.5272 °20.3808 °2--1.0115 °2
S0.0366 Å °0.0121 Å °0.0277 Å °-0.0669 Å °-0.0331 Å °-0.0398 Å °-0.0062 Å °0.0067 Å °-0.0035 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1301 - 1370
2X-RAY DIFFRACTION1A1201
3X-RAY DIFFRACTION1A814 - 1102

+
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