[English] 日本語
Yorodumi
- PDB-6ege: Crystal structure of the unphosphorylated IRAK4 kinase domain Bou... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ege
TitleCrystal structure of the unphosphorylated IRAK4 kinase domain Bound to a type I inhibitor
ComponentsInterleukin-1 receptor-associated kinase 4IRAK4
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Unphosphorylated / Inactive / SIGNALING PROTEIN / 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 / positive regulation of canonical NF-kappaB signal transduction / cellular response to lipopolysaccharide / endosome membrane / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / protein kinase binding / magnesium ion binding / cell surface / extracellular space / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
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-DL1 / Interleukin-1 receptor-associated kinase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.401 Å
AuthorsFerrao, R. / Liu, Q. / Wu, H.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) United States
CitationJournal: J.Biol.Chem. / Year: 2019
Title: Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor-associated kinase 4 (IRAK4).
Authors: Wang, L. / Ferrao, R. / Li, Q. / Hatcher, J.M. / Choi, H.G. / Buhrlage, S.J. / Gray, N.S. / Wu, H.
History
DepositionAug 19, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 13, 2019Provider: repository / Type: Initial release
Revision 1.1Aug 28, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID
Revision 1.2Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Mar 13, 2024Group: Advisory / Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)68,1914
Polymers67,4332
Non-polymers7592
Water12,106672
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: equilibrium centrifugation, light scattering
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2240 Å2
ΔGint-4 kcal/mol
Surface area24590 Å2
Unit cell
Length a, b, c (Å)70.888, 58.553, 76.101
Angle α, β, γ (deg.)90.00, 112.78, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Interleukin-1 receptor-associated kinase 4 / IRAK4 / IRAK-4 / Renal carcinoma antigen NY-REN-64


Mass: 33716.324 Da / Num. of mol.: 2 / Fragment: Protein kinase domain residues 164-460
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-DL1 / N-[2-methoxy-4-(morpholin-4-yl)phenyl]-6-(1H-pyrazol-5-yl)pyridine-2-carboxamide


Mass: 379.412 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H21N5O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 672 / 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: 2.16 Å3/Da / Density % sol: 43.04 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop / Details: 150 mM DL-Malic acid and 20% PEG3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X4A / Wavelength: 0.98 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Aug 5, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 1.4→37.559 Å / Num. obs: 110700 / % possible obs: 98.07 % / Redundancy: 7.5 % / CC1/2: 1 / Rmerge(I) obs: 0.053 / Net I/σ(I): 17.78
Reflection shellResolution: 1.4→1.45 Å / Redundancy: 7.4 % / Rmerge(I) obs: 0.92 / Mean I/σ(I) obs: 2.38 / Num. unique obs: 10742 / CC1/2: 0.85 / % possible all: 94.94

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementResolution: 1.401→37.559 Å / SU ML: 0.16 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 23.31
RfactorNum. reflection% reflection
Rfree0.2014 5562 5.02 %
Rwork0.1777 --
obs0.1789 110693 98.06 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.401→37.559 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4366 0 56 672 5094
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0084503
X-RAY DIFFRACTIONf_angle_d1.1676064
X-RAY DIFFRACTIONf_dihedral_angle_d14.9041711
X-RAY DIFFRACTIONf_chiral_restr0.064668
X-RAY DIFFRACTIONf_plane_restr0.005783
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.4012-1.41710.33261650.31713254X-RAY DIFFRACTION91
1.4171-1.43380.3021890.29553466X-RAY DIFFRACTION97
1.4338-1.45130.32631840.28673406X-RAY DIFFRACTION97
1.4513-1.46960.30041830.2773459X-RAY DIFFRACTION97
1.4696-1.4890.30211950.26843407X-RAY DIFFRACTION97
1.489-1.50940.30171930.26323481X-RAY DIFFRACTION97
1.5094-1.53090.28821850.24913440X-RAY DIFFRACTION97
1.5309-1.55380.29441980.24473468X-RAY DIFFRACTION97
1.5538-1.57810.23491850.24063450X-RAY DIFFRACTION98
1.5781-1.60390.2691920.23553447X-RAY DIFFRACTION98
1.6039-1.63160.24591780.22333510X-RAY DIFFRACTION97
1.6316-1.66130.26451760.22923462X-RAY DIFFRACTION98
1.6613-1.69320.24611820.22373483X-RAY DIFFRACTION98
1.6932-1.72780.25491830.22523506X-RAY DIFFRACTION98
1.7278-1.76530.25411920.21853483X-RAY DIFFRACTION98
1.7653-1.80640.26311830.21913502X-RAY DIFFRACTION98
1.8064-1.85160.25681710.21333516X-RAY DIFFRACTION98
1.8516-1.90160.23681930.19583508X-RAY DIFFRACTION99
1.9016-1.95760.21971830.18643548X-RAY DIFFRACTION99
1.9576-2.02080.18761840.17673505X-RAY DIFFRACTION99
2.0208-2.0930.20292090.17443528X-RAY DIFFRACTION99
2.093-2.17680.18931960.1663526X-RAY DIFFRACTION99
2.1768-2.27580.1851740.16383535X-RAY DIFFRACTION99
2.2758-2.39580.18791910.15993557X-RAY DIFFRACTION99
2.3958-2.54590.19121720.16233594X-RAY DIFFRACTION99
2.5459-2.74240.18171900.16073544X-RAY DIFFRACTION100
2.7424-3.01830.19321790.1613597X-RAY DIFFRACTION100
3.0183-3.45480.17261610.15553635X-RAY DIFFRACTION100
3.4548-4.35160.15271800.14543633X-RAY DIFFRACTION100
4.3516-37.57250.18712160.173681X-RAY DIFFRACTION100
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)
14.9851-1.52240.46751.74540.44530.77340.06560.1493-0.352-0.0359-0.0580.07230.07930.02350.00390.1365-0.0041-0.01510.12590.01770.1698-13.8092-22.7225-5.2139
25.18023.18153.30148.79862.4218.99560.08161.0576-0.1063-0.6371-0.0188-0.3641-0.0541-0.0920.01810.22810.08740.04610.3551-0.02120.22470.9677-22.5192-14.5406
30.7988-0.09140.0522.1081-0.5670.94210.12180.0904-0.1064-0.0382-0.15260.01590.02440.01040.02710.11490.0295-0.00060.1386-0.00530.117-5.0298-8.4645-8.5164
42.0256-0.2581-0.47911.6210.0862.80880.07670.30380.0562-0.2714-0.13290.0403-0.1122-0.0320.04620.20180.07650.00510.19530.0370.1175-3.5623.0091-22.7867
57.0141.0489-1.22642.42881.79564.06170.1807-0.09070.01550.277-0.60970.53140.263-0.54510.39660.2431-0.10840.01320.341-0.1390.4191-9.7805-28.4647-64.9509
62.88264.76011.62158.46340.56318.49830.4247-0.6356-1.15890.3232-0.4984-0.14080.2636-0.21510.13680.2608-0.0486-0.01040.26260.03330.36654.0745-29.7657-60.5672
78.773-1.4558-4.84984.75721.73588.9653-0.1978-0.9317-0.22470.6212-0.1630.21420.03580.62150.36090.3099-0.05660.0250.27870.03460.20034.9109-22.3484-57.9657
83.2044-0.858-1.08392.65430.33282.4265-0.02050.0323-0.23390.3227-0.23120.32670.5513-0.34280.26430.237-0.1150.02560.2335-0.0270.2395-3.1875-22.9501-62.9711
95.6220.9524-0.05350.7208-0.55264.8428-0.48890.052-0.11910.3207-0.60150.67940.3948-0.227-0.61510.1584-0.30360.41890.4642-0.34551.064-15.8537-16.4031-52.9582
107.09190.97641.88374.43523.97284.46680.05640.4396-0.5854-0.5756-0.19561.29390.1178-0.82510.2760.2635-0.0132-0.09150.2479-0.06550.382-11.2852-6.5716-62.7211
112.85561.95850.67833.62821.22011.88490.0116-0.0449-0.09780.08-0.0810.27390.1821-0.02250.09710.1587-0.01090.03670.1277-0.03560.19741.6869-13.138-61.6806
128.1674-1.6161-1.57782.5550.27182.36320.07080.25030.0944-0.19710.04430.0565-0.2043-0.0657-0.10760.179-0.0034-0.02070.11670.00220.0983-3.17822.1486-59.0147
135.9304-1.3937-0.08814.4516-0.57085.4271-0.277-0.1597-0.37010.23060.28310.70390.2639-0.4887-0.03050.1625-0.00850.04290.16550.04110.2174-10.8364-5.9975-49.7346
144.7962-0.97210.59754.9537-1.2345.1377-0.0530.1428-0.1525-0.26940.00790.19210.0236-0.30080.04650.1837-0.01550.00930.1308-0.02770.1689-0.3194-6.7027-62.4102
156.9119-1.0947-0.90883.8753-0.12283.2714-0.1119-0.3952-0.44940.71330.21150.40770.7235-0.76190.02370.376-0.11030.0810.32840.06320.2993-11.2205-11.2554-50.1375
166.4544-2.5988-3.45784.4860.30922.2224-0.325-0.2473-0.43260.30010.2140.43230.2938-0.34320.10450.23180.04970.03550.32680.04310.159-5.9695-6.6958-39.2186
173.19020.660.11352.42460.19662.4877-0.1766-0.5784-0.22450.13630.154-0.2544-0.08090.2203-0.04740.14720.0344-0.00250.23220.00430.13495.7837-2.7281-45.8319
181.65650.84530.40252.43730.73651.6820.0261-0.82140.38460.20490.0269-0.0704-0.45990.429-0.12930.3028-0.077-0.03090.4875-0.13590.276413.11896.1294-41.8135
193.3159-0.58440.30283.41230.83852.1743-0.1219-0.06510.6755-0.26140.2673-0.5095-0.38630.3234-0.1580.2398-0.0707-0.02140.1966-0.06020.28229.72077.8342-53.9875
202.23631.3997-2.25393.19092.03947.4219-0.3202-0.83060.19710.74520.48340.0597-0.3261-0.0029-0.15770.30930.1412-0.01570.338-0.07410.1896-5.55126.7729-40.5452
219.25513.8671-5.53661.9803-1.97797.9376-0.00510.17980.95210.06050.14630.1283-0.4665-0.1703-0.29010.25040.0216-0.04930.14350.01530.2821-3.877311.0297-56.5245
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'D' and (resid 162 through 224 )
2X-RAY DIFFRACTION2chain 'D' and (resid 225 through 239 )
3X-RAY DIFFRACTION3chain 'D' and (resid 240 through 332 )
4X-RAY DIFFRACTION4chain 'D' and (resid 333 through 457 )
5X-RAY DIFFRACTION5chain 'A' and (resid 165 through 177 )
6X-RAY DIFFRACTION6chain 'A' and (resid 178 through 184 )
7X-RAY DIFFRACTION7chain 'A' and (resid 185 through 197 )
8X-RAY DIFFRACTION8chain 'A' and (resid 198 through 226 )
9X-RAY DIFFRACTION9chain 'A' and (resid 227 through 239 )
10X-RAY DIFFRACTION10chain 'A' and (resid 240 through 247 )
11X-RAY DIFFRACTION11chain 'A' and (resid 248 through 284 )
12X-RAY DIFFRACTION12chain 'A' and (resid 285 through 304 )
13X-RAY DIFFRACTION13chain 'A' and (resid 305 through 313 )
14X-RAY DIFFRACTION14chain 'A' and (resid 314 through 327 )
15X-RAY DIFFRACTION15chain 'A' and (resid 328 through 335 )
16X-RAY DIFFRACTION16chain 'A' and (resid 347 through 365 )
17X-RAY DIFFRACTION17chain 'A' and (resid 366 through 395 )
18X-RAY DIFFRACTION18chain 'A' and (resid 396 through 413 )
19X-RAY DIFFRACTION19chain 'A' and (resid 414 through 436 )
20X-RAY DIFFRACTION20chain 'A' and (resid 437 through 446 )
21X-RAY DIFFRACTION21chain 'A' and (resid 447 through 459 )

+
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