[English] 日本語
Yorodumi
- PDB-4e4l: JAK1 kinase (JH1 domain) in complex with compound 30 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4e4l
TitleJAK1 kinase (JH1 domain) in complex with compound 30
ComponentsTyrosine-protein kinase JAK1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / o-phosphotyrosine / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / 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 ...protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / 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 / interleukin-10-mediated signaling pathway / interleukin-2-mediated signaling pathway / positive regulation of homotypic cell-cell adhesion / interleukin-15-mediated signaling pathway / Interleukin-15 signaling / Interleukin-12 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / growth hormone receptor binding / Interleukin-2 signaling / extrinsic component of cytoplasmic side of plasma membrane / Other interleukin signaling / Interleukin-20 family signaling / IFNG signaling activates MAPKs / Interleukin-6 signaling / type I interferon-mediated signaling pathway / interleukin-6-mediated signaling pathway / MAPK3 (ERK1) activation / positive regulation of sprouting angiogenesis / MAPK1 (ERK2) activation / Interleukin-10 signaling / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / cell surface receptor signaling pathway via JAK-STAT / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / Signaling by CSF3 (G-CSF) / Interleukin-7 signaling / non-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / Inactivation of CSF3 (G-CSF) signaling / cellular response to virus / Evasion by RSV of host interferon responses / ISG15 antiviral mechanism / positive regulation of protein localization to nucleus / cytoplasmic side of plasma membrane / cytokine-mediated signaling pathway / Interferon gamma signaling / Interferon alpha/beta signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell differentiation / cytoskeleton / protein phosphorylation / receptor complex / endosome / intracellular signal transduction / response to antibiotic / focal adhesion / ubiquitin protein ligase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / metal ion binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak1 / 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 Jak1 / 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. / 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-0NH / Tyrosine-protein kinase JAK1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsEigenbrot, C.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors.
Authors: Kulagowski, J.J. / Blair, W. / Bull, R.J. / Chang, C. / Deshmukh, G. / Dyke, H.J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / Harrison, T.K. / Hewitt, P.R. / Liimatta, M. / Hurley, C.A. / ...Authors: Kulagowski, J.J. / Blair, W. / Bull, R.J. / Chang, C. / Deshmukh, G. / Dyke, H.J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / Harrison, T.K. / Hewitt, P.R. / Liimatta, M. / Hurley, C.A. / Johnson, A. / Johnson, T. / Kenny, J.R. / Bir Kohli, P. / Maxey, R.J. / Mendonca, R. / Mortara, K. / Murray, J. / Narukulla, R. / Shia, S. / Steffek, M. / Ubhayakar, S. / Ultsch, M. / van Abbema, A. / Ward, S.I. / Waszkowycz, B. / Zak, M.
History
DepositionMar 13, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 30, 2012Provider: repository / Type: Initial release
Revision 1.1Jul 11, 2012Group: Database references
Revision 1.2Oct 30, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / struct_conn / 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_conn.pdbx_leaving_atom_flag / _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 JAK1
B: Tyrosine-protein kinase JAK1
E: Tyrosine-protein kinase JAK1
D: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)140,3208
Polymers138,9864
Non-polymers1,3344
Water9,944552
1
A: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,4133
Polymers34,7471
Non-polymers6672
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,0802
Polymers34,7471
Non-polymers3331
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
E: Tyrosine-protein kinase JAK1


Theoretical massNumber of molelcules
Total (without water)34,7471
Polymers34,7471
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,0802
Polymers34,7471
Non-polymers3331
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.837, 171.759, 87.821
Angle α, β, γ (deg.)90.00, 92.15, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2given(-0.999969, 0.000661, 0.007849), (-0.00061, -0.999979, 0.006455), (0.007853, 0.00645, 0.999948)-22.32482, 109.50098, -0.14042
3given(-0.999925, 0.011919, 0.002638), (-0.011902, -0.999908, 0.006509), (0.002715, 0.006477, 0.999975)-19.593, 111.16192, 43.55382
4given(0.99983, -0.017982, 0.004028), (0.017992, 0.999835, -0.00261), (-0.003981, 0.002682, 0.999988)-0.99012, -0.9524, 43.73676

-
Components

#1: Protein
Tyrosine-protein kinase JAK1 / Janus kinase 1 / JAK-1


Mass: 34746.594 Da / Num. of mol.: 4 / Fragment: protein kinase domain JH1, UNP residues 854-1154
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK1, JAK1A, JAK1B / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P23458, non-specific protein-tyrosine kinase
#2: Chemical
ChemComp-0NH / 1-[4-methyl-1-(methylsulfonyl)piperidin-4-yl]-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine


Mass: 333.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C15H19N5O2S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 552 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.32 Å3/Da / Density % sol: 47.05 %
Crystal growTemperature: 300 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: MES pH 5.5 30% PEG6000, VAPOR DIFFUSION, SITTING DROP, temperature 300K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 30, 2010
RadiationMonochromator: double-crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2→50 Å / Num. all: 80512 / Num. obs: 80512 / % possible obs: 94.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -2 / Redundancy: 3.2 % / Biso Wilson estimate: 26 Å2 / Rsym value: 0.07 / Net I/σ(I): 15
Reflection shellResolution: 2→2.07 Å / Mean I/σ(I) obs: 2.6 / Rsym value: 0.432 / % possible all: 90.3

-
Processing

Software
NameVersionClassification
BOSdata collection
PHASERphasing
REFMAC5.6.0117refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2→50 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.929 / SU B: 7.873 / SU ML: 0.118 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): -2 / ESU R: 0.204 / ESU R Free: 0.17 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22814 3725 4.6 %RANDOM
Rwork0.18957 ---
all0.19 80512 --
obs0.19138 76787 94.47 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 31.25 Å2
Baniso -1Baniso -2Baniso -3
1--0.65 Å2-0 Å20.12 Å2
2--0.19 Å2-0 Å2
3---0.47 Å2
Refinement stepCycle: LAST / Resolution: 2→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9166 0 92 552 9810
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.029623
X-RAY DIFFRACTIONr_bond_other_d0.0060.026716
X-RAY DIFFRACTIONr_angle_refined_deg1.2521.99813012
X-RAY DIFFRACTIONr_angle_other_deg0.844316393
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.79751145
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.66224.315438
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.401151785
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.5731556
X-RAY DIFFRACTIONr_chiral_restr0.1160.21375
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.02110515
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021909
LS refinement shellResolution: 2.001→2.109 Å / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.277 536 -
Rwork0.23 10443 -
obs--89.26 %
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)
11.09750.487-0.08471.0709-0.50982.12520.0248-0.12070.04660.179-0.01010.204-0.006-0.0588-0.01470.03970.00730.03790.04570.0070.0573-24.572926.51692.5777
21.2112-0.1363-0.06011.5988-0.15130.7689-0.05590.02040.1015-0.20060.0781-0.09360.01630.0498-0.02220.0297-0.01160.00660.02250.00540.0209-8.793734.4263-15.9976
31.11730.19930.38881.1880.73772.29170.0191-0.1355-0.03090.2230.013-0.1980.1769-0.032-0.03210.04890.0019-0.02420.02560.00280.07532.512682.90952.2067
41.21070.05480.25290.952-0.02360.6813-0.02240.002-0.058-0.09230.0848-0.0062-0.0094-0.011-0.06240.0157-0.00480.00770.0113-0.00230.0272-13.602774.9941-16.2996
50.95960.21460.72541.02380.84492.4849-0.0666-0.0147-0.16810.13190.0447-0.12160.0952-0.03750.02190.02890.00990.00930.02670.01370.09116.409784.3037-41.427
61.1804-0.04630.00212.1818-0.09230.6178-0.08440.0819-0.126-0.31010.13030.14870.0370.0042-0.04590.068-0.0118-0.00670.0257-0.00130.0559-10.083376.445-60.0784
71.139-0.0603-0.08261.0136-0.48911.9737-0.02370.05450.05530.14670.02870.2486-0.0471-0.0861-0.0050.0238-0.0030.03660.01990.00530.0737-23.167527.9389-41.2434
81.0271-0.3261-0.282.12420.06590.80220.05780.16320.1426-0.25740.0338-0.17-0.05-0.0969-0.09170.03390.00550.02640.06550.02840.0331-6.911835.4012-59.9013
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A865 - 959
2X-RAY DIFFRACTION2A960 - 1154
3X-RAY DIFFRACTION3B864 - 959
4X-RAY DIFFRACTION4B960 - 1154
5X-RAY DIFFRACTION5D864 - 959
6X-RAY DIFFRACTION6D960 - 1154
7X-RAY DIFFRACTION7E864 - 959
8X-RAY DIFFRACTION8E960 - 1154

+
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