[English] 日本語
Yorodumi
- PDB-7p5n: Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 interaction -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7p5n
TitlePyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 interaction
ComponentsKelch-like ECH-associated protein 1
KeywordsPROTEIN BINDING / protein ubiquitination / protein-protein interaction / oxidative stress
Function / homology
Function and homology information


cellular response to carbohydrate stimulus / KEAP1-NFE2L2 pathway / regulation of epidermal cell differentiation / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / Ub-specific processing proteases / negative regulation of response to oxidative stress / Cul3-RING ubiquitin ligase complex / centriolar satellite / ubiquitin-like ligase-substrate adaptor activity ...cellular response to carbohydrate stimulus / KEAP1-NFE2L2 pathway / regulation of epidermal cell differentiation / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / Ub-specific processing proteases / 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 / adherens junction / disordered domain specific binding / cellular response to oxidative stress / midbody / ubiquitin-dependent protein catabolic process / RNA polymerase II-specific DNA-binding transcription factor binding / in utero embryonic development / protein ubiquitination / negative regulation of gene expression / focal adhesion / regulation of DNA-templated transcription / endoplasmic reticulum / 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 / Kelch motif / 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 / Kelch motif / 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
Chem-5RQ / Kelch-like ECH-associated protein 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 1.89 Å
AuthorsDavies, T.G.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction.
Authors: Norton, D. / Bonnette, W.G. / Callahan, J.F. / Carr, M.G. / Griffiths-Jones, C.M. / Heightman, T.D. / Kerns, J.K. / Nie, H. / Rich, S.J. / Richardson, C. / Rumsey, W. / Sanchez, Y. / ...Authors: Norton, D. / Bonnette, W.G. / Callahan, J.F. / Carr, M.G. / Griffiths-Jones, C.M. / Heightman, T.D. / Kerns, J.K. / Nie, H. / Rich, S.J. / Richardson, C. / Rumsey, W. / Sanchez, Y. / Verdonk, M.L. / Willems, H.M.G. / Wixted, W.E. / Wolfe 3rd, L. / Woolford, A.J. / Wu, Z. / Davies, T.G.
History
DepositionJul 14, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 17, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 24, 2021Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jun 19, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
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)35,7503
Polymers35,2511
Non-polymers4992
Water5,080282
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area150 Å2
ΔGint-11 kcal/mol
Surface area11760 Å2
MethodPISA
Unit cell
Length a, b, c (Å)103.315, 103.315, 56.142
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61

-
Components

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


Mass: 35251.371 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(DE3) (bacteria) / References: UniProt: Q9Z2X8
#2: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#3: Chemical ChemComp-5RQ / 1-[3-[(1~{R},3~{S})-3-[(2~{R})-2-butylpyrrolidin-1-yl]carbonylcyclohexyl]phenyl]-5-cyclopropyl-pyrazole-4-carboxylic acid


Mass: 463.612 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H37N3O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 282 / 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: 2.45 Å3/Da / Density % sol: 49.87 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6
Details: 0.3M (NH4)2SO4 1M Li2SO4 0.1M pH=5.6 Na3 citrate/HCl

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-X / Wavelength: 1.54187 Å
DetectorType: RIGAKU SATURN 944 / Detector: CCD / Date: Oct 1, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54187 Å / Relative weight: 1
ReflectionResolution: 1.89→38.04 Å / Num. obs: 25757 / % possible obs: 94.8 % / Redundancy: 2.5 % / Rmerge(I) obs: 0.091 / Net I/σ(I): 6.7
Reflection shellResolution: 1.89→1.9 Å / Rmerge(I) obs: 0.344 / Num. unique obs: 167

-
Processing

Software
NameVersionClassification
REFMAC5.8.0222refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
SCALAdata scaling
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.89→38.04 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.943 / SU B: 6.471 / SU ML: 0.1 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.14 / ESU R Free: 0.136 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2159 1302 5 %RANDOM
Rwork0.1694 ---
obs0.1718 24514 94.44 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 93.52 Å2 / Biso mean: 27.827 Å2 / Biso min: 12.3 Å2
Baniso -1Baniso -2Baniso -3
1--0.28 Å2-0.14 Å2-0 Å2
2---0.28 Å20 Å2
3---0.9 Å2
Refinement stepCycle: final / Resolution: 1.89→38.04 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2213 0 71 282 2566
Biso mean--19.41 35.91 -
Num. residues----288
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0152310
X-RAY DIFFRACTIONr_bond_other_d0.0010.0171939
X-RAY DIFFRACTIONr_angle_refined_deg1.3621.7493148
X-RAY DIFFRACTIONr_angle_other_deg0.4961.7154551
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.0955289
X-RAY DIFFRACTIONr_dihedral_angle_2_deg25.36819.542118
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.41515.233322
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.5271521
X-RAY DIFFRACTIONr_chiral_restr0.0660.2284
X-RAY DIFFRACTIONr_gen_planes_refined0.0010.0212688
X-RAY DIFFRACTIONr_gen_planes_other00.02445
LS refinement shellResolution: 1.894→1.943 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.277 69 -
Rwork0.238 1332 -
all-1401 -
obs--70.37 %
Refinement TLS params.Method: refined / Origin x: 22.9153 Å / Origin y: 61.4897 Å / Origin z: 37.8987 Å
111213212223313233
T0.0237 Å20.0028 Å2-0.0186 Å2-0.0038 Å20.0069 Å2--0.0767 Å2
L2.2153 °2-0.4025 °2-0.5179 °2-3.2806 °20.2914 °2--1.146 °2
S-0.0263 Å °-0.0394 Å °-0.1023 Å °0.1476 Å °0.0455 Å °0.2393 Å °0.06 Å °0.0364 Å °-0.0192 Å °

+
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