[English] 日本語
Yorodumi
- PDB-8tvm: IRAK4 in complex with compound 24 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8tvm
TitleIRAK4 in complex with compound 24
ComponentsInterleukin-1 receptor-associated kinase 4
KeywordsTRANSFERASE/INHIBITOR / kinase / 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 / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Interleukin-1 receptor-associated kinase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsMetrick, C.M. / Chodaparambil, J.V.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Acs Med.Chem.Lett. / Year: 2024
Title: A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors.
Authors: Bolduc, P.N. / Pfaffenbach, M. / Evans, R. / Xin, Z. / Henry, K.L. / Gao, F. / Fang, T. / Silbereis, J. / Vera Rebollar, J. / Li, P. / Chodaparambil, J.V. / Metrick, C. / Peterson, E.A.
History
DepositionAug 18, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 26, 2024Provider: repository / Type: Initial release

-
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)140,5028
Polymers138,6324
Non-polymers1,8704
Water4,954275
1
A: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1252
Polymers34,6581
Non-polymers4671
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1252
Polymers34,6581
Non-polymers4671
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1252
Polymers34,6581
Non-polymers4671
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1252
Polymers34,6581
Non-polymers4671
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)136.380, 141.980, 87.780
Angle α, β, γ (deg.)90.000, 126.370, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z

-
Components

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


Mass: 34657.938 Da / Num. of mol.: 4
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-VDC / N-{1-[(1R,2R)-2-fluorocyclopropyl]-2-oxo-1,2-dihydropyridin-3-yl}-2-[(1R,4r)-1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl]-6-[(propan-2-yl)oxy]-2H-pyrazolo[3,4-b]pyridine-5-carboxamide


Mass: 467.493 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H26FN5O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 275 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.6 Å3/Da / Density % sol: 52.69 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: Sodium Malonate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 1M / Detector: PIXEL / Date: Dec 18, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. obs: 145187 / % possible obs: 93.3 % / Redundancy: 1.86 % / Biso Wilson estimate: 45.74 Å2 / CC1/2: 0.998 / Net I/σ(I): 9.12
Reflection shellResolution: 2.1→2.23 Å / Num. unique obs: 23404 / CC1/2: 0.588

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
XDSdata reduction
XDSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→48.52 Å / SU ML: 0.295 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 29.9701
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2465 3821 5 %
Rwork0.2212 72618 -
obs0.2225 76439 97.68 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 62.98 Å2
Refinement stepCycle: LAST / Resolution: 2.1→48.52 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8831 0 136 275 9242
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00439166
X-RAY DIFFRACTIONf_angle_d0.875612433
X-RAY DIFFRACTIONf_chiral_restr0.05351401
X-RAY DIFFRACTIONf_plane_restr0.00551579
X-RAY DIFFRACTIONf_dihedral_angle_d18.27973468
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1-2.130.42081390.40012649X-RAY DIFFRACTION97.18
2.13-2.150.37671410.37122675X-RAY DIFFRACTION97.04
2.15-2.180.33751390.33272669X-RAY DIFFRACTION97.47
2.18-2.220.31691400.30762674X-RAY DIFFRACTION97.4
2.22-2.250.32891430.30742694X-RAY DIFFRACTION97.16
2.25-2.280.31341410.29862675X-RAY DIFFRACTION97.71
2.28-2.320.29521380.28212650X-RAY DIFFRACTION97.18
2.32-2.360.29491420.28142688X-RAY DIFFRACTION98.06
2.36-2.40.30551420.26872699X-RAY DIFFRACTION97.8
2.4-2.450.28351420.25692694X-RAY DIFFRACTION97.96
2.45-2.50.28491420.25982691X-RAY DIFFRACTION97.96
2.5-2.550.29981390.26642651X-RAY DIFFRACTION97.96
2.55-2.610.30061440.2592716X-RAY DIFFRACTION98.08
2.61-2.680.30791430.27312717X-RAY DIFFRACTION97.95
2.68-2.750.2561420.26742711X-RAY DIFFRACTION98.24
2.75-2.830.30641420.26082693X-RAY DIFFRACTION98.4
2.83-2.920.30021410.24552673X-RAY DIFFRACTION98.05
2.92-3.030.26851410.24972693X-RAY DIFFRACTION97.79
3.03-3.150.28021440.23462726X-RAY DIFFRACTION98.09
3.15-3.290.26841410.24292677X-RAY DIFFRACTION98.29
3.29-3.470.28631420.22672722X-RAY DIFFRACTION98.39
3.47-3.680.21841430.20632704X-RAY DIFFRACTION98.14
3.68-3.970.21721410.19362689X-RAY DIFFRACTION97.52
3.97-4.370.20111420.16782694X-RAY DIFFRACTION97.39
4.37-50.17821420.1732689X-RAY DIFFRACTION97.12
5-6.30.22821410.20762684X-RAY DIFFRACTION96.61
6.3-48.520.20961440.18682721X-RAY DIFFRACTION96.59

+
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