[English] 日本語
Yorodumi
- PDB-6v6z: Crystal structure of N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-meth... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6v6z
TitleCrystal structure of N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine bound to human Keap1 Kelch domain
ComponentsKelch-like ECH-associated protein 1
KeywordsPROTEIN BINDING/INHIBITOR / Protein-protein interaction inhibitor / Keap1 / Nrf2 activator / Protein binding-inhibitor 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 / RNA polymerase II-specific DNA-binding transcription factor binding / in utero embryonic development / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / endoplasmic reticulum / nucleoplasm / identical protein binding / cytosol / cytoplasm
Similarity search - Function
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 / 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 / 6 Propeller / Neuraminidase / SKP1/BTB/POZ domain superfamily / Mainly Beta
Similarity search - Domain/homology
DITHIANE DIOL / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / FORMIC ACID / Chem-Q5Y / Kelch-like ECH-associated protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.6 Å
AuthorsLazzara, P.R. / David, B.P. / Ankireddy, A. / Richardson, B.G. / Dye, K. / Ratia, K.M. / Reddy, S.P. / Moore, T.W.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)1R01 AR069541-01A1 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)1R01 HL136946-01 United States
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors.
Authors: Lazzara, P.R. / Jain, A.D. / Maldonado, A.C. / Richardson, B. / Skowron, K.J. / David, B.P. / Siddiqui, Z. / Ratia, K.M. / Moore, T.W.
History
DepositionDec 6, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 29, 2020Provider: repository / Type: Initial release
Revision 1.1Apr 7, 2021Group: Derived calculations / Structure summary / Category: pdbx_struct_conn_angle / struct / struct_conn
Item: _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id ..._pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct.title / _struct_conn.pdbx_dist_value / _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.ptnr1_label_seq_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 / _struct_conn.ptnr2_symmetry
Revision 1.2Oct 11, 2023Group: 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
C: Kelch-like ECH-associated protein 1
D: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)132,02679
Polymers126,5024
Non-polymers5,52475
Water18,8621047
1
A: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,75716
Polymers31,6251
Non-polymers1,13215
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,05622
Polymers31,6251
Non-polymers1,43121
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,14021
Polymers31,6251
Non-polymers1,51420
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Kelch-like ECH-associated protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,07320
Polymers31,6251
Non-polymers1,44719
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)59.360, 75.543, 97.947
Angle α, β, γ (deg.)74.550, 77.540, 67.480
Int Tables number1
Space group name H-MP1

-
Components

-
Protein , 1 types, 4 molecules ABCD

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


Mass: 31625.381 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Escherichia coli (E. coli) / References: UniProt: Q14145

-
Non-polymers , 6 types, 1122 molecules

#2: Chemical...
ChemComp-FMT / FORMIC ACID


Mass: 46.025 Da / Num. of mol.: 61 / Source method: obtained synthetically / Formula: CH2O2
#3: Chemical
ChemComp-Q5Y / N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine


Mass: 556.607 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C26H24N2O8S2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-DTD / DITHIANE DIOL


Mass: 152.235 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H8O2S2
#6: Chemical ChemComp-DTT / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / 1,4-DITHIOTHREITOL


Mass: 154.251 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O2S2
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1047 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.07 Å3/Da / Density % sol: 59.92 %
Crystal growTemperature: 289 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 3.5-3.8 M sodium formate, pH 7

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.9787 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Jun 22, 2019
RadiationMonochromator: diamond(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9787 Å / Relative weight: 1
ReflectionResolution: 1.6→19.74 Å / Num. obs: 182432 / % possible obs: 92 % / Redundancy: 2 % / CC1/2: 0.999 / Rmerge(I) obs: 0.033 / Rpim(I) all: 0.033 / Rrim(I) all: 0.047 / Net I/σ(I): 10.5
Reflection shell

Diffraction-ID: 1 / Redundancy: 2 %

Resolution (Å)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.6-1.630.4631845892490.6650.4630.6541.694.3
8.76-19.730.017197010070.9980.0170.02426.683.2

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
REFMAC5.8.0238refinement
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1U6D

1u6d


Resolution: 1.6→19.73 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.956 / SU B: 1.823 / SU ML: 0.061 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.089 / ESU R Free: 0.086
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2104 9206 5 %RANDOM
Rwork0.1918 ---
obs0.1927 173224 91.99 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 69.34 Å2 / Biso mean: 23.41 Å2 / Biso min: 10.74 Å2
Baniso -1Baniso -2Baniso -3
1-1.36 Å20.11 Å2-0.52 Å2
2---0.77 Å20.37 Å2
3----0.21 Å2
Refinement stepCycle: final / Resolution: 1.6→19.73 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8747 0 359 1047 10153
Biso mean--32.39 32.31 -
Num. residues----1141
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.0129330
X-RAY DIFFRACTIONr_angle_refined_deg1.441.66312632
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.59351159
X-RAY DIFFRACTIONr_dihedral_angle_2_deg29.62820.31516
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.717151334
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.1541589
X-RAY DIFFRACTIONr_chiral_restr0.0980.21132
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.027382
LS refinement shellResolution: 1.6→1.642 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.326 718 -
Rwork0.307 13172 -
all-13890 -
obs--94.45 %

+
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