[English] 日本語
Yorodumi
- PDB-6zex: Keap1 kelch domain bound to a small molecule fragment -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6zex
TitleKeap1 kelch domain bound to a small molecule fragment
ComponentsKelch-like ECH-associated protein 1
KeywordsPEPTIDE BINDING PROTEIN / Keap1 / Nrf2 / Oxidative stress / Small molecule complex
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 / ubiquitin-dependent protein catabolic process / midbody / in utero embryonic development / proteasome-mediated ubiquitin-dependent protein catabolic process / RNA polymerase II-specific DNA-binding transcription factor binding / regulation of autophagy / protein ubiquitination / regulation of DNA-templated transcription / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / cytoplasm / cytosol
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
5-cyclopropyl-1-phenyl-pyrazole-4-carboxylic acid / Kelch-like ECH-associated protein 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.98 Å
AuthorsNarayanan, D. / Bach, A. / Gajhede, M.
Funding support Denmark, 1items
OrganizationGrant numberCountry
LundbeckfondenR190-2014-3710 Denmark
Citation
Journal: J.Med.Chem. / Year: 2021
Title: Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds.
Authors: Pallesen, J.S. / Narayanan, D. / Tran, K.T. / Solbak, S.M.O. / Marseglia, G. / Sorensen, L.M.E. / Hoj, L.J. / Munafo, F. / Carmona, R.M.C. / Garcia, A.D. / Desu, H.L. / Brambilla, R. / ...Authors: Pallesen, J.S. / Narayanan, D. / Tran, K.T. / Solbak, S.M.O. / Marseglia, G. / Sorensen, L.M.E. / Hoj, L.J. / Munafo, F. / Carmona, R.M.C. / Garcia, A.D. / Desu, H.L. / Brambilla, R. / Johansen, T.N. / Popowicz, G.M. / Sattler, M. / Gajhede, M. / Bach, A.
History
DepositionJun 16, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 14, 2021Provider: repository / Type: Initial release
Revision 1.1May 5, 2021Group: 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 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)34,0598
Polymers33,3621
Non-polymers6977
Water81145
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1050 Å2
ΔGint14 kcal/mol
Surface area12220 Å2
MethodPISA
Unit cell
Length a, b, c (Å)104.094, 104.094, 54.835
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

#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
#2: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#3: Chemical ChemComp-QHN / 5-cyclopropyl-1-phenyl-pyrazole-4-carboxylic acid


Mass: 228.247 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H12N2O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 45 / 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: 2.72 Å3/Da / Density % sol: 54.75 %
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: ESRF / Beamline: MASSIF-3 / Wavelength: 0.9677 Å
DetectorType: DECTRIS EIGER X 4M / Detector: PIXEL / Date: Jul 2, 2018 / Details: CRL
RadiationMonochromator: C(110) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9677 Å / Relative weight: 1
ReflectionResolution: 1.98→34.07 Å / Num. obs: 23735 / % possible obs: 99.79 % / Redundancy: 13.8 % / Biso Wilson estimate: 34.14 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.1111 / Rpim(I) all: 0.03065 / Rrim(I) all: 0.1154 / Net I/σ(I): 15.06
Reflection shellResolution: 1.98→2.051 Å / Redundancy: 8.3 % / Rmerge(I) obs: 1.579 / Mean I/σ(I) obs: 1.17 / Num. unique obs: 2360 / CC1/2: 0.506 / Rpim(I) all: 0.5776 / Rrim(I) all: 1.685 / % possible all: 99.37

-
Processing

Software
NameVersionClassification
XDSv Jan 26, 2018data scaling
PHASER1.13_2998phasing
PHENIX1.13_2998refinement
XDSv Jan 26, 2018data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5FNU

5fnu


Resolution: 1.98→34.07 Å / SU ML: 0.2572 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 28.6621 / Stereochemistry target values: GeoStd + Monomer Library
RfactorNum. reflection% reflectionSelection details
Rfree0.2323 1131 4.77 %Random
Rwork0.1954 22599 --
obs0.1971 23730 99.82 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 54.69 Å2
Refinement stepCycle: LAST / Resolution: 1.98→34.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2219 0 41 45 2305
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01232315
X-RAY DIFFRACTIONf_angle_d1.03893147
X-RAY DIFFRACTIONf_chiral_restr0.0684329
X-RAY DIFFRACTIONf_plane_restr0.0075413
X-RAY DIFFRACTIONf_dihedral_angle_d12.60111339
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.98-2.070.36581220.36022842X-RAY DIFFRACTION99.46
2.07-2.180.31581600.29452771X-RAY DIFFRACTION99.9
2.18-2.320.27141470.2272799X-RAY DIFFRACTION99.9
2.32-2.490.26811580.22122785X-RAY DIFFRACTION99.83
2.49-2.750.24631460.20832822X-RAY DIFFRACTION99.9
2.75-3.140.23421340.20712819X-RAY DIFFRACTION99.86
3.14-3.960.22941490.18762836X-RAY DIFFRACTION99.97
3.96-34.070.17691150.14832925X-RAY DIFFRACTION99.87
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)
15.68369649141-2.598411350751.620461421292.96503678988-2.154342524598.78068582402-0.128663368302-0.27912550077-0.500659181129-0.266700951676-0.1854896411330.1443973287410.765632856364-0.4208641985920.3129814255320.316437332651-0.0215727534579-0.002833583040820.376405783542-0.1098483562040.695156057754-42.4156789108-22.1101201748-7.37161667158
24.63504443915-1.12647742260.8038795086552.445790323110.1401668449931.771832634040.2281386866530.456547502078-0.875398893205-0.461995668785-0.2770928112960.6204327357580.013737350376-0.04900754232230.03920540525470.3981902979430.0654568709218-0.07215472951780.351190778945-0.1188384390750.479569430164-40.3342043277-17.7624296058-12.1471710702
34.624989197990.287370315911.409689700641.607765107011.585203163855.899280285280.007241283794760.26034146324-0.616520846564-0.180108734959-0.05180297270520.1201258143620.230635065470.09506552708250.05419054220570.3991895809580.05734443366960.01231294855210.307183708291-0.09069222829420.561374150608-31.3555422036-22.4057640958-8.94897576242
43.25743770664-1.50236308290.9009360162284.622124373240.9060619055541.3330266824-0.0159135896815-0.0383216231726-0.03108052417780.1090811746570.170004472878-0.305833243747-0.03404609912050.183972292038-0.1682570673750.2803586555230.00598839573220.03247779992210.302296023570.006612266855890.336784396946-27.4511054236-8.3028799075-0.174307822039
54.81255908889-1.0907200999-2.20695659772.17477680785-1.761184388245.63977739429-0.258303557847-0.5493089418320.1865246459790.4465242329920.28158254148-0.1078190029140.1024129839110.093361624772-0.01415047245650.3687562344330.0570234077519-0.03392575041280.334664444883-0.04549701290020.303037274712-30.8587585313-1.775486378578.94952195075
64.40761666089-0.9188771906290.6883998491592.442071025861.361800936041.55961861951-0.182752247313-0.344604439489-0.04738940194220.3367764922230.1493424472040.3155691373110.026074854321-0.1604589322690.0448264926410.4055572196140.02854908919170.1253481053150.371719136790.02308264228060.412502418185-45.4007288414-2.553430533777.37422991276
74.98391367018-0.575063104953-2.19481697874.899950848310.6711214639745.59077584964-0.1509265954740.0407486674719-0.675141279587-0.0718862847076-0.133447071560.9366066656680.0952210813768-0.4048770675720.2362455930450.260549924560.00457378060320.01940723842390.31784664431-0.01568077391780.576073159667-50.4777036784-9.93303196918-1.79241076666
81.185531229820.8524049066120.04330570399481.414962615751.278666294332.327146320690.1425429440640.133758568889-1.318155166350.130199108447-0.52781181951.458965937010.279340525339-0.06503790199880.1931608766040.329354923812-0.03092485526940.1967909202220.2676261276190.02621215794770.712577852648-53.2747979666-13.36024280240.60837958066
93.12936509706-1.082107707620.451309499464.659768543030.404808107670.3129800108450.06662373732750.496420285815-0.80537277338-0.30920822755-0.2796810223590.8627865582420.0871242660813-0.3905703652370.2928962764280.3569145856530.00383154566411-0.05934399808130.401189851913-0.09953088673930.609189670219-48.4593856539-15.4928637093-8.77690575592
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 325 through 341 )
2X-RAY DIFFRACTION2chain 'A' and (resid 342 through 377 )
3X-RAY DIFFRACTION3chain 'A' and (resid 378 through 406 )
4X-RAY DIFFRACTION4chain 'A' and (resid 407 through 475 )
5X-RAY DIFFRACTION5chain 'A' and (resid 476 through 500 )
6X-RAY DIFFRACTION6chain 'A' and (resid 501 through 547 )
7X-RAY DIFFRACTION7chain 'A' and (resid 548 through 569 )
8X-RAY DIFFRACTION8chain 'A' and (resid 570 through 589 )
9X-RAY DIFFRACTION9chain 'A' and (resid 590 through 613 )

+
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