[English] 日本語
Yorodumi
- PDB-5ebz: Crystal structure of human IKK1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ebz
TitleCrystal structure of human IKK1
ComponentsInhibitor of nuclear factor kappa-B kinase subunit alpha
KeywordsTransferase/transferase inhibitor / kinase / inhibitor / Transferase-transferase inhibitor complex
Function / homology
Function and homology information


response to acetate / IkappaB kinase / IkappaB kinase activity / IKBKB deficiency causes SCID / IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) / response to cholecystokinin / IkappaB kinase complex / I-kappaB phosphorylation / transferrin receptor binding / IkBA variant leads to EDA-ID ...response to acetate / IkappaB kinase / IkappaB kinase activity / IKBKB deficiency causes SCID / IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) / response to cholecystokinin / IkappaB kinase complex / I-kappaB phosphorylation / transferrin receptor binding / IkBA variant leads to EDA-ID / CD40 receptor complex / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / RIP-mediated NFkB activation via ZBP1 / response to hydroperoxide / AKT phosphorylates targets in the cytosol / toll-like receptor 4 signaling pathway / negative regulation of NF-kappaB transcription factor activity / non-canonical NF-kappaB signal transduction / Constitutive Signaling by AKT1 E17K in Cancer / TRAF6 mediated NF-kB activation / Rho protein signal transduction / skeletal muscle contraction / positive regulation of interferon-alpha production / anatomical structure morphogenesis / canonical NF-kappaB signal transduction / response to amino acid / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / striated muscle cell differentiation / tumor necrosis factor-mediated signaling pathway / cellular response to cadmium ion / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / TNFR1-induced NF-kappa-B signaling pathway / NIK-->noncanonical NF-kB signaling / Regulation of NF-kappa B signaling / Dectin-1 mediated noncanonical NF-kB signaling / Activation of NF-kappaB in B cells / Regulation of TNFR1 signaling / TAK1-dependent IKK and NF-kappa-B activation / response to virus / NOD1/2 Signaling Pathway / PKR-mediated signaling / cytoplasmic side of plasma membrane / response to toxic substance / CLEC7A (Dectin-1) signaling / cellular response to virus / FCERI mediated NF-kB activation / cellular response to reactive oxygen species / Interleukin-1 signaling / Downstream TCR signaling / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / scaffold protein binding / positive regulation of canonical NF-kappaB signal transduction / response to lipopolysaccharide / protein kinase activity / response to xenobiotic stimulus / inflammatory response / immune response / protein heterodimerization activity / protein phosphorylation / innate immune response / protein serine/threonine kinase activity / protein-containing complex binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / positive regulation of DNA-templated transcription / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / cytoplasm / cytosol
Similarity search - Function
I-kappa-kinase-beta NEMO binding domain / IKBKB, scaffold dimerization domain / IKBKB, scaffold dimerization domain superfamily / I-kappa-kinase-beta NEMO binding domain / IQBAL scaffold dimerization domain / I-kappa-kinase-beta NEMO binding domain / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain ...I-kappa-kinase-beta NEMO binding domain / IKBKB, scaffold dimerization domain / IKBKB, scaffold dimerization domain superfamily / I-kappa-kinase-beta NEMO binding domain / IQBAL scaffold dimerization domain / I-kappa-kinase-beta NEMO binding domain / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
2-azanyl-5-phenyl-3-(4-sulfamoylphenyl)benzamide / Inhibitor of nuclear factor kappa-B kinase subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 4.5 Å
AuthorsPolley, S. / Passos, D. / Huang, D. / Biswas, T. / Verma, I. / Lyumkis, D. / Ghosh, G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)CA141722 United States
CitationJournal: Cell Rep / Year: 2016
Title: Structural Basis for the Activation of IKK1/α.
Authors: Smarajit Polley / Dario Oliveira Passos / De-Bin Huang / Maria Carmen Mulero / Anup Mazumder / Tapan Biswas / Inder M Verma / Dmitry Lyumkis / Gourisankar Ghosh /
Abstract: Distinct signaling pathways activate the NF-κB family of transcription factors. The canonical NF-κB-signaling pathway is mediated by IκB kinase 2/β (IKK2/β), while the non-canonical pathway ...Distinct signaling pathways activate the NF-κB family of transcription factors. The canonical NF-κB-signaling pathway is mediated by IκB kinase 2/β (IKK2/β), while the non-canonical pathway depends on IKK1/α. The structural and biochemical bases for distinct signaling by these otherwise highly similar IKKs are unclear. We report single-particle cryoelectron microscopy (cryo-EM) and X-ray crystal structures of human IKK1 in dimeric (∼150 kDa) and hexameric (∼450 kDa) forms. The hexamer, which is the representative form in the crystal but comprises only ∼2% of the particles in solution by cryo-EM, is a trimer of IKK1 dimers. While IKK1 hexamers are not detectable in cells, the surface that supports hexamer formation is critical for IKK1-dependent cellular processing of p100 to p52, the hallmark of non-canonical NF-κB signaling. Comparison of this surface to that in IKK2 indicates significant divergence, and it suggests a fundamental role for this surface in signaling by these kinases through distinct pathways.
History
DepositionOct 20, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 2, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 21, 2016Group: Database references
Revision 1.2Sep 6, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Dec 4, 2019Group: Author supporting evidence / Data collection / Category: chem_comp / pdbx_audit_support
Item: _chem_comp.type / _pdbx_audit_support.funding_organization
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Mar 6, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / struct_conn
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Inhibitor of nuclear factor kappa-B kinase subunit alpha
B: Inhibitor of nuclear factor kappa-B kinase subunit alpha
C: Inhibitor of nuclear factor kappa-B kinase subunit alpha
D: Inhibitor of nuclear factor kappa-B kinase subunit alpha
E: Inhibitor of nuclear factor kappa-B kinase subunit alpha
F: Inhibitor of nuclear factor kappa-B kinase subunit alpha
G: Inhibitor of nuclear factor kappa-B kinase subunit alpha
H: Inhibitor of nuclear factor kappa-B kinase subunit alpha
I: Inhibitor of nuclear factor kappa-B kinase subunit alpha
J: Inhibitor of nuclear factor kappa-B kinase subunit alpha
K: Inhibitor of nuclear factor kappa-B kinase subunit alpha
L: Inhibitor of nuclear factor kappa-B kinase subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)933,78052
Polymers901,76312
Non-polymers32,01740
Water00
1
A: Inhibitor of nuclear factor kappa-B kinase subunit alpha
B: Inhibitor of nuclear factor kappa-B kinase subunit alpha
C: Inhibitor of nuclear factor kappa-B kinase subunit alpha
D: Inhibitor of nuclear factor kappa-B kinase subunit alpha
E: Inhibitor of nuclear factor kappa-B kinase subunit alpha
F: Inhibitor of nuclear factor kappa-B kinase subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)466,89026
Polymers450,8826
Non-polymers16,00820
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area32070 Å2
ΔGint-2 kcal/mol
Surface area181470 Å2
MethodPISA
2
G: Inhibitor of nuclear factor kappa-B kinase subunit alpha
H: Inhibitor of nuclear factor kappa-B kinase subunit alpha
I: Inhibitor of nuclear factor kappa-B kinase subunit alpha
J: Inhibitor of nuclear factor kappa-B kinase subunit alpha
K: Inhibitor of nuclear factor kappa-B kinase subunit alpha
L: Inhibitor of nuclear factor kappa-B kinase subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)466,89026
Polymers450,8826
Non-polymers16,00820
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area31390 Å2
ΔGint7 kcal/mol
Surface area180120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)174.510, 186.940, 275.830
Angle α, β, γ (deg.)90.00, 98.84, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
Inhibitor of nuclear factor kappa-B kinase subunit alpha / IkappaB kinase / Conserved helix-loop-helix ubiquitous kinase / I-kappa-B kinase 1 / IKK1 / Nuclear ...IkappaB kinase / Conserved helix-loop-helix ubiquitous kinase / I-kappa-B kinase 1 / IKK1 / Nuclear factor NF-kappa-B inhibitor kinase alpha / NFKBIKA / Transcription factor 16 / TCF-16


Mass: 75146.945 Da / Num. of mol.: 12 / Mutation: S176E, S180E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CHUK, IKKA, TCF16 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O15111, IkappaB kinase
#2: Polysaccharide...
2,3-di-O-sulfo-alpha-D-glucopyranose-(1-6)-alpha-D-glucopyranose-(1-6)-2,4-di-O-sulfo-alpha-D-glucopyranose


Type: oligosaccharide / Mass: 824.690 Da / Num. of mol.: 24 / Source method: obtained synthetically
DescriptorTypeProgram
WURCS=2.0/3,3,2/[a2122h-1a_1-5_2*OSO/3=O/3=O_4*OSO/3=O/3=O][a2122h-1a_1-5][a2122h-1a_1-5_2*OSO/3=O/3=O_3*OSO/3=O/3=O]/1-2-3/a6-b1_b6-c1WURCSPDB2Glycan 1.1.0
[][a-D-Glcp2SO34SO3]{[(6+1)][a-D-Glcp]{[(6+1)][a-D-Glcp2SO33SO3]{}}}LINUCSPDB-CARE
#3: Polysaccharide
[(2S,3R,4S,5S,6R)-6-(hydroxymethyl)-2,4-bis(oxidanyl)-5-oxidanylsulfanyloxy-oxan-3-yl] hydrogen ...[(2S,3R,4S,5S,6R)-6-(hydroxymethyl)-2,4-bis(oxidanyl)-5-oxidanylsulfanyloxy-oxan-3-yl] hydrogen sulfate-(1-6)-(2S,3R,4R,5S,6R)-6-(hydroxymethyl)-5-oxidanylsulfanyloxy-oxane-2,3,4-triol-(1-6)-2-O-sulfo-alpha-D-glucopyranose-(1-6)-[(2R,3R,4R,5R,6S)-2-(hydroxymethyl)-5,6-bis(oxidanyl)-3-oxidanylsulfanyloxy-oxan-4-yl] hydrogen sulfate-(1-6)-[(2S,3R,4S,5R,6R)-6-(hydroxymethyl)-2,5-bis(oxidanyl)-4-oxidanylsulfanyloxy-oxan-3-yl] hydrogen sulfate-(1-6)-[(2R,3R,4R,5R,6S)-2-(hydroxymethyl)-5,6-bis(oxidanyl)-3-oxidanylsulfanyloxy-oxan-4-yl] hydrogen sulfate-(1-6)-2,4-di-O-sulfo-alpha-D-glucopyranose


Type: oligosaccharide / Mass: 1953.762 Da / Num. of mol.: 4 / Source method: obtained synthetically
DescriptorTypeProgram
WURCS=2.0/6,7,6/[a2122h-1a_1-5_2*OSO/3=O/3=O_4*OSO/3=O/3=O][a2122h-1a_1-5_3*OSO/3=O/3=O_4*OSO][a2122h-1a_1-5_2*OSO/3=O/3=O_3*OSO][a2122h-1a_1-5_2*OSO/3=O/3=O][a2122h-1a_1-5_4*OSO][a2122h-1a_1-5_2*OSO/3=O/3=O_4*OSO]/1-2-3-2-4-5-6/a6-b1_b6-c1_c6-d1_d6-e1_e6-f1_f6-g1WURCSPDB2Glycan 1.1.0
[][a-D-Glcp2SO34SO3]{[(6+1)][a-D-Glcp3SO3]{[(6+1)][a-D-Glcp2SO3]{[(6+1)][a-D-Glcp3SO3]{[(6+1)][a-D-Glcp2SO3]{[(6+1)][a-D-Glcp]{[(6+1)][a-D-Glcp2SO3]{}}}}}}}LINUCSPDB-CARE
#4: Chemical
ChemComp-5TL / 2-azanyl-5-phenyl-3-(4-sulfamoylphenyl)benzamide


Mass: 367.422 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C19H17N3O3S

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.93 Å3/Da / Density % sol: 75.05 %
Crystal growTemperature: 277 K / Method: evaporation / Details: PEG, Dextran Sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97927 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 4, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97927 Å / Relative weight: 1
ReflectionResolution: 4.5→45 Å / Num. obs: 99808 / % possible obs: 95.5 % / Observed criterion σ(F): 1 / Redundancy: 7 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 5.2
Reflection shellResolution: 4.5→4.58 Å / Redundancy: 6.8 % / Rmerge(I) obs: 0.81 / Mean I/σ(I) obs: 1.5 / % possible all: 88

-
Processing

Software
NameVersionClassification
CNS1.3refinement
HKL-2000data collection
HKL-2000data scaling
PDB_EXTRACT3.15data extraction
HKL-2000data reduction
MOLREPphasing
RefinementResolution: 4.5→29.94 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 95567.81 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 1 / Details: BULK SOLVENT MODEL USED
RfactorNum. reflection% reflectionSelection details
Rfree0.276 2851 4 %RANDOM
Rwork0.238 ---
obs0.238 70648 68.1 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 236.747 Å2 / ksol: 0.28 e/Å3
Displacement parametersBiso mean: 267.7 Å2
Baniso -1Baniso -2Baniso -3
1-78.8 Å20 Å2-3.73 Å2
2---55.52 Å20 Å2
3----23.28 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.91 Å0.82 Å
Luzzati d res low-5 Å
Luzzati sigma a0.62 Å1.39 Å
Refinement stepCycle: LAST / Resolution: 4.5→29.94 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms63156 0 1976 0 65132
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.005
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg0.8
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d20.1
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d1.39
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it
X-RAY DIFFRACTIONc_mcangle_it
X-RAY DIFFRACTIONc_scbond_it
X-RAY DIFFRACTIONc_scangle_it
LS refinement shellResolution: 4.5→4.78 Å / Rfactor Rfree error: 0.024 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.474 381 4.6 %
Rwork0.462 7985 -
obs--48.8 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1CNS_TOPPAR/protein_rep.paramCNS_TOPPAR/protein.top
X-RAY DIFFRACTION2CNS_TOPPAR/dna-rna_rep.paramCNS_TOPPAR/dna-rna.top
X-RAY DIFFRACTION3CNS_TOPPAR/water_rep.paramCNS_TOPPAR/water.top
X-RAY DIFFRACTION4CNS_TOPPAR/ion.paramCNS_TOPPAR/ion.top
X-RAY DIFFRACTION5gls3.paramgls3d.top
X-RAY DIFFRACTION6CNS_TOPPAR/xnn7.paramxnn.top
X-RAY DIFFRACTION7XNM.parinh.top

+
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