[English] 日本語
Yorodumi
- PDB-7uyv: Crystal structure of JAK3 kinase domain in complex with compound 25 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7uyv
TitleCrystal structure of JAK3 kinase domain in complex with compound 25
ComponentsTyrosine-protein kinase JAK3
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / non-receptor tyrosine-protein kinase JAK3 / 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 glycoprotein biosynthetic process / 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 glycoprotein biosynthetic process / 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 / Interleukin-15 signaling / negative regulation of thymocyte apoptotic process / growth hormone receptor binding / Interleukin-2 signaling / extrinsic component of cytoplasmic side of plasma membrane / regulation of receptor signaling pathway via JAK-STAT / 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 / Interleukin receptor SHC signaling / cell surface receptor signaling pathway via JAK-STAT / Interleukin-7 signaling / B cell differentiation / non-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / cytoplasmic side of plasma membrane / cytokine-mediated signaling pathway / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / Interleukin-4 and Interleukin-13 signaling / regulation of apoptotic process / Potential therapeutics for SARS / adaptive immune response / cell differentiation / cytoskeleton / endosome / intracellular signal transduction / 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-OV5 / Tyrosine-protein kinase JAK3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.15 Å
AuthorsToms, A.V. / Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. ...Toms, A.V. / Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Shelley, M. / Wester, R.T. / Westlin, W. / Mc Elwee, J.J. / Miao, W. / Edmondson, S.D. / Massee, C.E.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2022
Title: Potent and selective TYK2-JH1 inhibitors highly efficacious in rodent model of psoriasis.
Authors: Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Toms, A.V. / Shelley, M. / Wester, ...Authors: Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Toms, A.V. / Shelley, M. / Wester, R.T. / Westlin, W. / McElwee, J.J. / Miao, W. / Edmondson, S.D. / Masse, C.E.
History
DepositionMay 7, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 24, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / 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 JAK3
B: Tyrosine-protein kinase JAK3
C: Tyrosine-protein kinase JAK3
D: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)134,8349
Polymers133,1034
Non-polymers1,7315
Water7,891438
1
A: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7002
Polymers33,2761
Non-polymers4241
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7002
Polymers33,2761
Non-polymers4241
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7002
Polymers33,2761
Non-polymers4241
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Tyrosine-protein kinase JAK3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7353
Polymers33,2761
Non-polymers4592
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)57.074, 114.166, 106.086
Angle α, β, γ (deg.)90.000, 97.540, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 33275.871 Da / Num. of mol.: 4 / Fragment: KINASE DOMAIN
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-OV5 / 6-{[(2M)-2-(2-chloro-6-fluorophenyl)-5-oxo-5H-pyrrolo[3,4-b]pyridin-4-yl]amino}-N-ethylpyridine-3-carboxamide


Mass: 423.828 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H15ClFN5O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 438 / 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: 2.7 Å3/Da / Density % sol: 53.3 %
Crystal growTemperature: 298 K / Method: vapor diffusion
Details: Crystals of human JAK3 in complex with the ligand were prepared according to established protocols

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 2, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→105.17 Å / Num. obs: 70329 / % possible obs: 96 % / Redundancy: 2.8 % / Rmerge(I) obs: 0.065 / Net I/σ(I): 14.04
Reflection shellResolution: 2.15→2.4 Å / Redundancy: 2.8 % / Rmerge(I) obs: 0.434 / Mean I/σ(I) obs: 2.76 / Num. unique obs: 19754 / Rrim(I) all: 0.539 / % possible all: 96.3

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
XSCALEdata scaling
PHASERphasing
REFMAC5.2.0005refinement
PDB_EXTRACT3.27data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 2.15→105.17 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.911 / SU B: 17.207 / SU ML: 0.222 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.268 / ESU R Free: 0.214 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2629 1558 2.2 %RANDOM
Rwork0.2206 ---
obs0.2215 68763 96.04 %-
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 max: 123.93 Å2 / Biso mean: 39.447 Å2 / Biso min: 2 Å2
Baniso -1Baniso -2Baniso -3
1--1.18 Å20 Å20.13 Å2
2---2.17 Å20 Å2
3---3.39 Å2
Refinement stepCycle: final / Resolution: 2.15→105.17 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8984 0 116 438 9538
Biso mean--19.53 18.18 -
Num. residues----1115
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0229248
X-RAY DIFFRACTIONr_bond_other_d0.0020.028387
X-RAY DIFFRACTIONr_angle_refined_deg1.0851.99812569
X-RAY DIFFRACTIONr_angle_other_deg1.247319384
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.1551129
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.96622.822404
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.455151507
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.5571576
X-RAY DIFFRACTIONr_chiral_restr0.0610.21339
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.0210296
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021966
X-RAY DIFFRACTIONr_nbd_refined0.1550.21557
X-RAY DIFFRACTIONr_nbd_other0.1420.27796
X-RAY DIFFRACTIONr_nbtor_refined0.1560.24391
X-RAY DIFFRACTIONr_nbtor_other0.0660.24771
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.0810.2397
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.0640.215
X-RAY DIFFRACTIONr_symmetry_vdw_other0.1090.2121
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.0680.217
LS refinement shellResolution: 2.15→2.206 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.349 120 -
Rwork0.313 5082 -
all-5202 -
obs--96.57 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.16470.65350.72119.29990.26871.4403-0.0277-0.0655-0.34780.25710.0762-1.03470.02010.3185-0.0484-0.1989-0.0053-0.0565-0.1564-0.0043-0.079919.477-37.05457.398
21.31980.55440.51774.1897-0.25073.4075-0.03070.32550.1011-0.4922-0.0156-0.3357-0.03420.16440.0464-0.17070.04630.0254-0.1222-0.0033-0.18426.136-24.75439.482
32.6453-1.8674-0.28478.9214-0.40621.9213-0.06190.19320.2544-0.22510.0003-0.9387-0.04420.41370.0615-0.20390.00080.0425-0.1349-0.0111-0.1466-8.8320.98747.588
41.61840.4816-0.21113.6344-0.34832.85120.0501-0.3116-0.11440.4645-0.0889-0.21430.07180.09640.0387-0.1721-0.0453-0.0209-0.11460.0109-0.187-22.277-11.06466.04
54.8145-1.3202-0.0647.76491.61112.4196-0.0841-0.03980.4922-0.1410.2198-0.7715-0.35810.1837-0.1357-0.04930.00520.0234-0.04580.0023-0.1312-16.79240.349104.805
62.15960.5578-1.32413.6241-1.11855.1367-0.02-0.1686-0.12970.2105-0.057-0.132-0.059-0.09520.077-0.149-0.0215-0.0197-0.0439-0.0001-0.1537-29.15123.756119.565
74.45640.94160.78647.33432.03242.5905-0.05090.0617-0.39840.17860.3127-1.02060.36380.4417-0.2619-0.07660.01-0.06250.0024-0.02170.004311.9581.436105.247
82.9487-0.09061.585.22120.7894.34710.04150.35560.0418-0.81830.0929-0.3977-0.3140.1015-0.13440.0013-0.00360.0835-0.04880.0203-0.217-1.317.98190.591
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A814 - 904
2X-RAY DIFFRACTION2A905 - 1100
3X-RAY DIFFRACTION3B814 - 904
4X-RAY DIFFRACTION4B905 - 1100
5X-RAY DIFFRACTION5C812 - 904
6X-RAY DIFFRACTION6C905 - 1100
7X-RAY DIFFRACTION7D814 - 904
8X-RAY DIFFRACTION8D905 - 1100

+
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