[English] 日本語
Yorodumi
- PDB-4xs2: Irak4-inhibitor co-structure -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xs2
TitleIrak4-inhibitor co-structure
ComponentsInterleukin-1 receptor-associated kinase 4
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / KINASE / PHOSPHATASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


IRAK4 deficiency (TLR5) / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / neutrophil migration / interleukin-33-mediated signaling pathway / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding ...IRAK4 deficiency (TLR5) / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / neutrophil migration / interleukin-33-mediated signaling pathway / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / toll-like receptor signaling pathway / extrinsic component of plasma membrane / JNK cascade / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / positive regulation of smooth muscle cell proliferation / cytokine-mediated signaling pathway / Interleukin-1 signaling / PIP3 activates AKT signaling / kinase activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / positive regulation of canonical NF-kappaB signal transduction / endosome membrane / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / protein kinase binding / cell surface / magnesium ion binding / extracellular space / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Interleukin-1 receptor-associated kinase 4 / IRAK4, Death domain / Death-like domain superfamily / 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 / Serine/Threonine protein kinases, catalytic domain ...Interleukin-1 receptor-associated kinase 4 / IRAK4, Death domain / Death-like domain superfamily / 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 / Serine/Threonine protein kinases, catalytic domain / 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-42P / Interleukin-1 receptor-associated kinase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.73 Å
AuthorsFischmann, T.O.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2015
Title: Discovery and hit-to-lead optimization of 2,6-diaminopyrimidine inhibitors of interleukin-1 receptor-associated kinase 4.
Authors: McElroy, W.T. / Michael Seganish, W. / Jason Herr, R. / Harding, J. / Yang, J. / Yet, L. / Komanduri, V. / Prakash, K.C. / Lavey, B. / Tulshian, D. / Greenlee, W.J. / Sondey, C. / Fischmann, T.O. / Niu, X.
History
DepositionJan 21, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 13, 2015Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2017Group: Database references / Derived calculations ...Database references / Derived calculations / Refinement description / Source and taxonomy
Category: citation / entity_src_gen ...citation / entity_src_gen / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag / _pdbx_struct_oper_list.symmetry_operation
Revision 1.2Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Interleukin-1 receptor-associated kinase 4
B: Interleukin-1 receptor-associated kinase 4
C: Interleukin-1 receptor-associated kinase 4
D: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)137,7458
Polymers135,8254
Non-polymers1,9204
Water59433
1
A: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4362
Polymers33,9561
Non-polymers4801
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4362
Polymers33,9561
Non-polymers4801
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4362
Polymers33,9561
Non-polymers4801
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4362
Polymers33,9561
Non-polymers4801
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)143.970, 139.990, 87.620
Angle α, β, γ (deg.)90.000, 125.470, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein
Interleukin-1 receptor-associated kinase 4 / IRAK-4 / Renal carcinoma antigen NY-REN-64


Mass: 33956.195 Da / Num. of mol.: 4 / Fragment: UNP residues 160-460
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF21
References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-42P / (1R,2S,3R,5R)-3-({5-(1,3-benzothiazol-2-yl)-6-chloro-2-[(3-methoxypropyl)amino]pyrimidin-4-yl}amino)-5-(hydroxymethyl)cyclopentane-1,2-diol


Mass: 479.980 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H26ClN5O4S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 33 / 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: 2.62 Å3/Da / Density % sol: 53.06 %
Crystal growTemperature: 289 K / Method: vapor diffusion, hanging drop / pH: 6.4
Details: 1.80 to 2.0 M Sodium Malonate pH 7.4, 0.2 M Sodium Acetate, 25 mM Hexamminecobalt(III)chloride, 0.05%w/v Pluronic-F-68
PH range: 7.4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: CHESS / Beamline: A1 / Wavelength: 0.9769 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Dec 15, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9769 Å / Relative weight: 1
ReflectionResolution: 2.75→50 Å / Num. obs: 36077 / % possible obs: 96.1 % / Redundancy: 3 % / Biso Wilson estimate: 64.22 Å2 / Rmerge(I) obs: 0.067 / Rpim(I) all: 0.045 / Rrim(I) all: 0.081 / Χ2: 0.895 / Net I/av σ(I): 13.332 / Net I/σ(I): 11.6 / Num. measured all: 107286
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.75-2.82.80.44918240.8310.3150.5510.93596.5
2.8-2.852.80.35617840.8950.2470.4350.97496.6
2.85-2.92.80.30618090.9430.2120.3740.91396.1
2.9-2.962.80.25117900.9580.1720.3061.00295.4
2.96-3.032.80.21617720.9570.1480.2630.93895.1
3.03-3.12.90.17217680.9810.1170.2090.9695.3
3.1-3.172.90.15217980.9880.1030.1840.94495.6
3.17-3.262.90.14118020.9920.0940.171.01195.9
3.26-3.362.90.11817780.9920.0790.1420.93996.2
3.36-3.4630.10618280.9870.0710.1280.91696.6
3.46-3.5930.0917870.9910.060.1080.9196.4
3.59-3.7330.0818210.9930.0530.0960.94496.8
3.73-3.93.10.0718190.9940.0460.0840.84597.7
3.9-4.113.10.05818300.9960.0380.0690.80897.1
4.11-4.363.10.05118270.9970.0330.0610.81796.9
4.36-4.73.10.04718210.9970.030.0560.78197
4.7-5.173.10.04318200.9980.0280.0510.77497
5.17-5.923.20.04818240.9970.0310.0570.7996.6
5.92-7.463.10.04118070.9980.0270.0490.86595.7
7.46-5030.03517680.9970.0240.0420.92991.9

-
Processing

Software
NameVersionClassification
BUSTER2.11.5refinement
DENZOdata reduction
SCALEPACKdata scaling
PDB_EXTRACT3.15data extraction
BUSTER-TNTphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2NRU

2nru


Resolution: 2.73→31.47 Å / Cor.coef. Fo:Fc: 0.8514 / Cor.coef. Fo:Fc free: 0.837 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 1.819 / SU Rfree Blow DPI: 0.38
RfactorNum. reflection% reflectionSelection details
Rfree0.285 1817 5.07 %RANDOM
Rwork0.264 ---
obs0.2651 35870 95.57 %-
Displacement parametersBiso max: 194.42 Å2 / Biso mean: 71.26 Å2 / Biso min: 3 Å2
Baniso -1Baniso -2Baniso -3
1--14.2534 Å20 Å2-18.0612 Å2
2--18.6291 Å20 Å2
3----4.3757 Å2
Refine analyzeLuzzati coordinate error obs: 0.491 Å
Refinement stepCycle: final / Resolution: 2.73→31.47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8888 0 161 0 9049
Biso mean--80.96 --
Num. residues----1131
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d3972SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes262HARMONIC2
X-RAY DIFFRACTIONt_gen_planes2591HARMONIC5
X-RAY DIFFRACTIONt_it17842HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1201SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact18853SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d17842HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg32168HARMONIC20.97
X-RAY DIFFRACTIONt_omega_torsion2.5
X-RAY DIFFRACTIONt_other_torsion16.68
LS refinement shellResolution: 2.73→2.81 Å / Total num. of bins used: 18
RfactorNum. reflection% reflection
Rfree0.2889 155 5.41 %
Rwork0.2762 2709 -
all0.2769 2864 -
obs--95.57 %

+
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://pdbjlvh1.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