[English] 日本語
Yorodumi
- PDB-6z6a: Keap1 macrocycle complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6z6a
TitleKeap1 macrocycle complex
ComponentsKelch-like ECH-associated protein 1
KeywordsLIGASE / macrocycle / complex
Function / homology
Function and homology information


regulation of epidermal cell differentiation / Nuclear events mediated by NFE2L2 / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity / cellular response to interleukin-4 / inclusion body / regulation of autophagy / actin filament ...regulation of epidermal cell differentiation / Nuclear events mediated by NFE2L2 / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity / cellular response to interleukin-4 / inclusion body / regulation of autophagy / actin filament / negative regulation of DNA-binding transcription factor activity / disordered domain specific binding / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / cellular response to oxidative stress / midbody / ubiquitin-dependent protein catabolic process / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / endoplasmic reticulum / 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 / Kelch repeat type 1 / Kelch motif / 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 / Kelch repeat type 1 / Kelch motif / 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
Chem-Q9E / Kelch-like ECH-associated protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.37 Å
AuthorsJohansson, P.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Mining Natural Products for Macrocycles to Drug Difficult Targets.
Authors: Begnini, F. / Poongavanam, V. / Over, B. / Castaldo, M. / Geschwindner, S. / Johansson, P. / Tyagi, M. / Tyrchan, C. / Wissler, L. / Sjo, P. / Schiesser, S. / Kihlberg, J.
History
DepositionMay 28, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 30, 2020Provider: repository / Type: Initial release
Revision 1.1Feb 10, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 2.0Feb 17, 2021Group: Derived calculations / Non-polymer description ...Derived calculations / Non-polymer description / Source and taxonomy / Structure summary
Category: chem_comp / entity ...chem_comp / entity / entity_src_gen / pdbx_entity_nonpoly
Item: _chem_comp.formula / _chem_comp.formula_weight ..._chem_comp.formula / _chem_comp.formula_weight / _chem_comp.name / _chem_comp.pdbx_synonyms / _entity.formula_weight / _entity.pdbx_description / _entity_src_gen.pdbx_host_org_ncbi_taxonomy_id / _entity_src_gen.pdbx_host_org_scientific_name / _pdbx_entity_nonpoly.name
Revision 2.1Jan 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
B: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,6795
Polymers64,1302
Non-polymers5493
Water3,279182
1
A: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,6144
Polymers32,0651
Non-polymers5493
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Kelch-like ECH-associated protein 1


Theoretical massNumber of molelcules
Total (without water)32,0651
Polymers32,0651
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)75.650, 75.800, 203.130
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Kelch-like ECH-associated protein 1 / Cytosolic inhibitor of Nrf2 / INrf2 / Kelch-like protein 19


Mass: 32064.867 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q14145
#2: Chemical ChemComp-Q9E / (5S,8R)-8-[[(2S)-1-ethanoylpyrrolidin-2-yl]carbonylamino]-N,N-dimethyl-7,11-bis(oxidanylidene)-10-oxa-3-thia-6-azabicyclo[10.4.0]hexadeca-1(16),12,14-triene-5-carboxamide / (5~{S},8~{R})-8-[[(2~{S})-1-ethanoyl-2,3-dihydropyrrol-2-yl]carbonylamino]-~{N},~{N}-dimethyl-7,11-bis(oxidanylidene)-10-oxa-3-thia-6-azabicyclo[10.4.0]hexadeca-1(16),12,14-triene-5-carboxamide


Mass: 490.573 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H30N4O6S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 182 / 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: 4.54 Å3/Da / Density % sol: 72.91 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 200 nL of protein (11-13 mg / mL) and 200 nL of well solution (3.7 to 4.1 M ammonium acetate, 0.09 M sodium acetate pH 4.6 and 10 mM cadmium chloride).

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 1.07227 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Feb 23, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.07227 Å / Relative weight: 1
ReflectionResolution: 2.37→47.37 Å / Num. obs: 48272 / % possible obs: 99.9 % / Redundancy: 6.5 % / Biso Wilson estimate: 80.94 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.077 / Rpim(I) all: 0.033 / Rrim(I) all: 0.084 / Net I/σ(I): 15.4 / Num. measured all: 312117 / Scaling rejects: 43
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.37-2.456.21.492904146620.5270.6481.6281.399.9
9.18-47.3760.02757209480.9990.0120.0341.799

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimless0.6.2data scaling
PHASERphasing
BUSTER2.11.7refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1ZGK

1zgk


Resolution: 2.37→47.37 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.934 / SU R Cruickshank DPI: 0.178 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.18 / SU Rfree Blow DPI: 0.153 / SU Rfree Cruickshank DPI: 0.153
RfactorNum. reflection% reflectionSelection details
Rfree0.209 2356 4.89 %RANDOM
Rwork0.192 ---
obs0.193 48155 99.7 %-
Displacement parametersBiso max: 151.36 Å2 / Biso mean: 70 Å2 / Biso min: 46.76 Å2
Baniso -1Baniso -2Baniso -3
1-6.4853 Å20 Å20 Å2
2---5.2305 Å20 Å2
3----1.2548 Å2
Refine analyzeLuzzati coordinate error obs: 0.32 Å
Refinement stepCycle: final / Resolution: 2.37→47.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4372 0 36 182 4590
Biso mean--77.88 67.98 -
Num. residues----570
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1484SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes791HARMONIC5
X-RAY DIFFRACTIONt_it4515HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion561SEMIHARMONIC5
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_contact5011SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4515HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg6152HARMONIC21.16
X-RAY DIFFRACTIONt_omega_torsion3.87
X-RAY DIFFRACTIONt_other_torsion17.35
LS refinement shellResolution: 2.37→2.43 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2497 189 5.47 %
Rwork0.2331 3269 -
all0.234 3458 -
obs--98.67 %
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)
13.05710.7584-0.2371.35790.0050.9158-0.07280.29310.154-0.05940.10630.0329-0.1486-0.1095-0.0335-0.3689-0.0110.0312-0.2459-0.0737-0.3392-28.773622.3809-11.8883
21.79371.20670.5732.43480.53441.76420.2163-0.22120.00330.1635-0.2927-0.06120.1173-0.02270.0764-0.3041-0.04930.1334-0.3744-0.037-0.327-2.98329.1302-38.7674
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A325 - 609
2X-RAY DIFFRACTION2{ B|* }B325 - 609

+
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