[English] 日本語
Yorodumi
- PDB-9hwu: Crystal structure of the Keap1 Kelch domain in complex with the s... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9hwu
TitleCrystal structure of the Keap1 Kelch domain in complex with the small molecule UCAB#1004 at 1.40 Angstrom resolution
ComponentsKelch-like ECH-associated protein 1
KeywordsPEPTIDE BINDING PROTEIN / Keap1 / Nrf2 / Oxidative stress / Inhibitor
Function / homology
Function and homology information


regulation of epidermal cell differentiation / Neddylation / Ub-specific processing proteases / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / ubiquitin-like ligase-substrate adaptor activity / transcription regulator inhibitor activity / inclusion body ...regulation of epidermal cell differentiation / Neddylation / Ub-specific processing proteases / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / ubiquitin-like ligase-substrate adaptor activity / transcription regulator inhibitor activity / inclusion body / cellular response to interleukin-4 / actin filament / centriolar satellite / disordered domain specific binding / cellular response to oxidative stress / midbody / ubiquitin-dependent protein catabolic process / in utero embryonic development / proteasome-mediated ubiquitin-dependent protein catabolic process / RNA polymerase II-specific DNA-binding transcription factor binding / protein ubiquitination / regulation of autophagy / regulation of DNA-templated transcription / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Kelch-like ECH-associated protein 1 / : / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / Kelch motif / Kelch / Kelch repeat type 1 / Kelch-type beta propeller ...Kelch-like ECH-associated protein 1 / : / BTB-kelch protein / BTB/Kelch-associated / BTB And C-terminal Kelch / BTB And C-terminal Kelch / Kelch motif / Kelch / Kelch repeat type 1 / Kelch-type beta propeller / BTB/POZ domain / BTB domain profile. / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / SKP1/BTB/POZ domain superfamily
Similarity search - Domain/homology
: / Kelch-like ECH-associated protein 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å
AuthorsNarayanan, D. / Bach, A. / Gajhede, M.
Funding support Denmark, 1items
OrganizationGrant numberCountry
LundbeckfondenR366-2021-270 Denmark
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2025
Title: Fragment-Based Drug Discovery of Novel High-affinity, Selective, and Anti-inflammatory Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction.
Authors: Lin, C. / Narayanan, D. / Barreca, M. / Poulsen, C. / da Costa, L.S. / Chen, X. / Wichman, K.G. / Charley, C.A. / Lindsay, J.L. / Dezfouli, M. / Vlissari, D. / Mortensen, T.S. / Chan, C.B. / ...Authors: Lin, C. / Narayanan, D. / Barreca, M. / Poulsen, C. / da Costa, L.S. / Chen, X. / Wichman, K.G. / Charley, C.A. / Lindsay, J.L. / Dezfouli, M. / Vlissari, D. / Mortensen, T.S. / Chan, C.B. / Wang, J. / Richardson, W. / Manning, C.E. / Chen, Z. / Zang, J. / Kack, H. / Gajhede, M. / Bullock, A.N. / Blake, D.J. / Olagnier, D. / Bach, A.
History
DepositionJan 6, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 3, 2025Provider: repository / Type: Initial release
Revision 1.1Oct 1, 2025Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Oct 8, 2025Group: Database references / Category: citation / citation_author
Item: _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,76214
Polymers33,3621
Non-polymers1,39913
Water3,621201
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, Monomer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2000 Å2
ΔGint-57 kcal/mol
Surface area12140 Å2
Unit cell
Length a, b, c (Å)102.997, 102.997, 54.641
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61
Space group name HallP61
Symmetry operation#1: x,y,z
#2: x-y,x,z+1/6
#3: y,-x+y,z+5/6
#4: -y,x-y,z+1/3
#5: -x+y,-x,z+2/3
#6: -x,-y,z+1/2

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Kelch-like ECH-associated protein 1 / Cytosolic inhibitor of Nrf2 / INrf2


Mass: 33362.297 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Keap1, Inrf2, Kiaa0132
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: Q9Z2X8

-
Non-polymers , 5 types, 214 molecules

#2: Chemical ChemComp-A1IXY / (3~{S})-3-(1,3-benzodioxol-5-yl)-3-[7-[2-(cyclohexylamino)-2-oxidanylidene-ethoxy]naphthalen-2-yl]propanoic acid


Mass: 475.533 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H29NO6 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#5: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 201 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.63 Å3/Da / Density % sol: 53.28 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6
Details: 0.5 M AMMONIUM SULFATE, 0.1 M SODIUM CITRATE TRIBASIC DIHYDRATE PH 5.6 AND 1.0 M LITHIUM SULFATE MONOHYDRATE

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: MAX IV / Beamline: BioMAX / Wavelength: 0.9762 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 28, 2022
RadiationMonochromator: Si (111), double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9762 Å / Relative weight: 1
ReflectionResolution: 1.4→46.59 Å / Num. obs: 64697 / % possible obs: 99.2 % / Redundancy: 20.7 % / Biso Wilson estimate: 16.14 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.151 / Rpim(I) all: 0.034 / Rrim(I) all: 0.155 / Χ2: 1.01 / Net I/σ(I): 11.2 / Num. measured all: 1338757
Reflection shellResolution: 1.4→1.42 Å / % possible obs: 96.9 % / Redundancy: 20.3 % / Rmerge(I) obs: 2.34 / Num. measured all: 66228 / Num. unique obs: 3263 / CC1/2: 0.721 / Rpim(I) all: 0.522 / Rrim(I) all: 2.399 / Χ2: 1.09 / Net I/σ(I) obs: 1.4

-
Processing

Software
NameVersionClassification
XDS20230630data reduction
Aimless0.7.7data scaling
PHASER2.8.3phasing
PHENIX1.20.1_4487refinement
PDB_EXTRACTV4.2data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.4→44.6 Å / SU ML: 0.141 / Cross valid method: FREE R-VALUE / σ(F): 0.71 / Phase error: 20.672
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1745 3175 4.91 %
Rwork0.1627 61438 -
obs0.1633 64613 99.11 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 21.46 Å2
Refinement stepCycle: LAST / Resolution: 1.4→44.6 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2235 0 81 201 2517
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00862479
X-RAY DIFFRACTIONf_angle_d1.11313387
X-RAY DIFFRACTIONf_chiral_restr0.0978346
X-RAY DIFFRACTIONf_plane_restr0.0102447
X-RAY DIFFRACTIONf_dihedral_angle_d10.3666374
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.4-1.420.29261220.26072614X-RAY DIFFRACTION96.78
1.42-1.440.27221430.24212603X-RAY DIFFRACTION97.62
1.44-1.470.23591320.23332651X-RAY DIFFRACTION98.24
1.47-1.490.24131330.21892661X-RAY DIFFRACTION98.66
1.49-1.520.23531330.20962628X-RAY DIFFRACTION97.7
1.52-1.550.22341330.20972629X-RAY DIFFRACTION99.21
1.55-1.580.26911390.19732668X-RAY DIFFRACTION98.73
1.58-1.610.21371270.18792647X-RAY DIFFRACTION98.4
1.61-1.650.20151460.17292650X-RAY DIFFRACTION98.97
1.65-1.690.1921300.16632677X-RAY DIFFRACTION99.5
1.69-1.740.19141290.15682659X-RAY DIFFRACTION98.9
1.74-1.790.16011600.15342638X-RAY DIFFRACTION99.15
1.79-1.850.19861310.1542672X-RAY DIFFRACTION99.29
1.85-1.910.17491530.15452651X-RAY DIFFRACTION99.47
1.91-1.990.16421340.14452689X-RAY DIFFRACTION99.61
1.99-2.080.16681250.14432715X-RAY DIFFRACTION99.79
2.08-2.190.17611200.1422706X-RAY DIFFRACTION99.68
2.19-2.330.17051440.14622687X-RAY DIFFRACTION99.93
2.33-2.510.16911280.15272715X-RAY DIFFRACTION99.96
2.51-2.760.151390.16432689X-RAY DIFFRACTION100
2.76-3.160.15451470.1652718X-RAY DIFFRACTION100
3.16-3.980.1651470.15412725X-RAY DIFFRACTION100
3.98-44.60.16411800.16352746X-RAY DIFFRACTION99.97
Refinement TLS params.Method: refined / Origin x: 38.1651241363 Å / Origin y: -11.0654201741 Å / Origin z: 2.59848513393 Å
111213212223313233
T0.132084768911 Å2-0.00379820873691 Å20.00214622172728 Å2-0.110277388037 Å2-0.0223557615259 Å2--0.112201900964 Å2
L0.918335676461 °20.273494941218 °20.0844823316784 °2-0.890610244107 °2-0.279689050875 °2--0.587393722111 °2
S0.0397476232097 Å °-0.0239707857295 Å °-0.084602915947 Å °0.0279561680343 Å °-0.0390028048545 Å °-0.0488054290396 Å °0.0262019791183 Å °0.0150339945393 Å °0.000306555504319 Å °
Refinement TLS groupSelection details: all

+
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