[English] 日本語
Yorodumi
- PDB-8sce: Crystal structure of IRAK4-HSA complexed with N-[(2R)-2-FLUORO-3-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8sce
TitleCrystal structure of IRAK4-HSA complexed with N-[(2R)-2-FLUORO-3-HYDROXY-3-METHYLBUTYL]-6-[(5-FLUOROPYRI-YL)AMINO]-4-[(PROPAN-2-YL)AMINO]PYRIDINE-3-CARBOXAMIDE
ComponentsInterleukin-1 receptor-associated kinase 4
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase / IRAK4 / ligand / 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 / interleukin-33-mediated signaling pathway / neutrophil migration / 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 / interleukin-33-mediated signaling pathway / neutrophil migration / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding / interleukin-1-mediated signaling pathway / extrinsic component of plasma membrane / IRAK4 deficiency (TLR2/4) / MyD88-dependent toll-like receptor signaling pathway / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / toll-like receptor signaling pathway / JNK cascade / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / lipopolysaccharide-mediated signaling pathway / positive regulation of smooth muscle cell proliferation / cytokine-mediated signaling pathway / Interleukin-1 signaling / kinase activity / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / eukaryotic translation initiation factor 2alpha kinase activity / positive regulation of canonical NF-kappaB signal transduction / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / endosome membrane / intracellular signal transduction / 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 / cytosol / cytoplasm
Similarity search - Function
Interleukin-1 receptor-associated kinase 4 / IRAK4, Death domain / : / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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: 1.89 Å
AuthorsMuckelbauer, J.K. / Ghosh, K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: The Discovery of IRAK4 Inhibitor Clinical Candidates BMS-986126 and BMS-986147 for the Treatment of Autoimmune Diseases
Authors: Kumar, S.R. / Dudhgoankar, S. / Santella, J.B. / Paidi, V.R.R. / Nair, S. / Sistla, R. / Wu, H. / Gardner, D.S. / Stachura, S. / Cavallaro, C.L. / Brown, G.D. / Pitts, W.J. / Kempson, J. / ...Authors: Kumar, S.R. / Dudhgoankar, S. / Santella, J.B. / Paidi, V.R.R. / Nair, S. / Sistla, R. / Wu, H. / Gardner, D.S. / Stachura, S. / Cavallaro, C.L. / Brown, G.D. / Pitts, W.J. / Kempson, J. / Tebben, A.J. / Tokarski, J.S. / Zhu, X. / Carman, J.A. / Foster, K. / Caceres Cortes, J. / Everlof, G. / Galella, M.A. / Sarjeant, A. / Holloway, D.A. / Fan, L. / Li, X. / Chaudhry, C. / Locke, G. / Chimalakondra, A. / Mariappan, T.T. / Ruepp, S. / Elzinga, P.A. / Saxena, A. / Xie, D. / Kiefer, S.E. / Yan, C. / Newitt, J.A. / Ghosh, K. / Anumula, R.K. / Sack, J.S. / Tino, J.A. / Carter, P.H. / Hynes, J. / Duncia, J.V.
History
DepositionApr 5, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 12, 2025Provider: 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
D: Interleukin-1 receptor-associated kinase 4
E: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)138,95611
Polymers137,0904
Non-polymers1,8667
Water9,566531
1
A: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,6672
Polymers34,2731
Non-polymers3941
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)34,6672
Polymers34,2731
Non-polymers3941
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
D: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,7633
Polymers34,2731
Non-polymers4902
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
E: Interleukin-1 receptor-associated kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,8594
Polymers34,2731
Non-polymers5873
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)135.812, 140.235, 86.949
Angle α, β, γ (deg.)90.00, 126.14, 90.00
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: 34272.566 Da / Num. of mol.: 4 / Fragment: KINASE DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-ZVD / N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[(5-fluoropyrimidin-4-yl)amino]-4-[(propan-2-yl)amino]pyridine-3-carboxamide


Mass: 394.419 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H24F2N6O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 531 / 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: 2.44 Å3/Da / Density % sol: 49.57 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: Crystallization conditions: 2.6 to 2.9 M ammonium sulphate in 25 mM HEPES pH 6.4 to 7.5 at 293K
PH range: 6.4-7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.979 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Dec 5, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.88→50 Å / Num. obs: 102853 / % possible obs: 98.2 % / Redundancy: 3.9 % / Rpim(I) all: 0.046 / Net I/av σ(I): 17.2 / Net I/σ(I): 8.3
Reflection shellResolution: 1.88→1.95 Å / Redundancy: 3.9 % / Mean I/σ(I) obs: 1.8 / Num. unique obs: 10120 / CC1/2: 0.695 / Rpim(I) all: 0.498 / Χ2: 1.079 / % possible all: 97.3

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
BUSTER2.11.5refinement
HKL-2000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.89→43 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.924 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.13
RfactorNum. reflection% reflectionSelection details
Rfree0.228 5120 4.99 %RANDOM
Rwork0.202 ---
obs0.204 102690 98 %-
Displacement parametersBiso mean: 37.11 Å2
Baniso -1Baniso -2Baniso -3
1--4.359 Å20 Å2-5.581 Å2
2--7.474 Å20 Å2
3----3.115 Å2
Refine analyzeLuzzati coordinate error obs: 0.249 Å
Refinement stepCycle: LAST / Resolution: 1.89→43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8767 0 127 531 9425
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.019154HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.0612479HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3128SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes227HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1406HARMONIC5
X-RAY DIFFRACTIONt_it9154HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3
X-RAY DIFFRACTIONt_other_torsion16.72
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1217SEMIHARMONIC5
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_contact11183SEMIHARMONIC4
LS refinement shellResolution: 1.89→1.94 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2947 362 4.99 %
Rwork0.2847 6887 -
all0.285 7249 -
obs--98.03 %

+
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