[English] 日本語
Yorodumi
- PDB-3sfi: Ethionamide Boosters Part 2: Combining Bioisosteric Replacement a... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3sfi
TitleEthionamide Boosters Part 2: Combining Bioisosteric Replacement and Structure-Based Drug Design to Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors.
ComponentsTranscriptional regulatory repressor protein (TETR-family)
KeywordsTRANSCRIPTION REPRESSOR/INHIBITOR / TETR-FAMILY / TRANSCRITPTIONAL REGULATORY REPRESSOR / INHIBITOR / DNA / DNA BINDING PROTEIN / TRANSCRIPTION REPRESSOR-INHIBITOR complex
Function / homology
Function and homology information


transcription cis-regulatory region binding / DNA-binding transcription factor activity / response to antibiotic / negative regulation of DNA-templated transcription / regulation of DNA-templated transcription / cytosol
Similarity search - Function
: / Transcriptional regulator EthR, C-terminal domain / Tetracycline Repressor, domain 2 / Tetracyclin repressor-like, C-terminal domain superfamily / Tetracycline Repressor; domain 2 / Bacterial regulatory proteins, tetR family / DNA-binding HTH domain, TetR-type / TetR-type HTH domain profile. / Homeodomain-like / Homeobox-like domain superfamily ...: / Transcriptional regulator EthR, C-terminal domain / Tetracycline Repressor, domain 2 / Tetracyclin repressor-like, C-terminal domain superfamily / Tetracycline Repressor; domain 2 / Bacterial regulatory proteins, tetR family / DNA-binding HTH domain, TetR-type / TetR-type HTH domain profile. / Homeodomain-like / Homeobox-like domain superfamily / Arc Repressor Mutant, subunit A / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-3SF / HTH-type transcriptional regulator EthR / HTH-type transcriptional regulator EthR
Similarity search - Component
Biological speciesMycobacterium tuberculosis (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.31 Å
AuthorsFlipo, M. / Desroses, M. / Lecat-Guillet, N. / Villemagne, B. / Blondiaux, N. / Leroux, F. / Piveteau, C. / Mathys, V. / Flament, M.P. / Siepmann, J. ...Flipo, M. / Desroses, M. / Lecat-Guillet, N. / Villemagne, B. / Blondiaux, N. / Leroux, F. / Piveteau, C. / Mathys, V. / Flament, M.P. / Siepmann, J. / Villeret, V. / Wohlkonig, A. / Wintjens, R. / Soror, S.H. / Christophe, T. / Jeon, H.K. / Locht, C. / Brodin, P. / D prez, B. / Baulard, A.R. / Willand, N.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors.
Authors: Flipo, M. / Desroses, M. / Lecat-Guillet, N. / Villemagne, B. / Blondiaux, N. / Leroux, F. / Piveteau, C. / Mathys, V. / Flament, M.P. / Siepmann, J. / Villeret, V. / Wohlkonig, A. / ...Authors: Flipo, M. / Desroses, M. / Lecat-Guillet, N. / Villemagne, B. / Blondiaux, N. / Leroux, F. / Piveteau, C. / Mathys, V. / Flament, M.P. / Siepmann, J. / Villeret, V. / Wohlkonig, A. / Wintjens, R. / Soror, S.H. / Christophe, T. / Jeon, H.K. / Locht, C. / Brodin, P. / Deprez, B. / Baulard, A.R. / Willand, N.
History
DepositionJun 13, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 7, 2011Provider: repository / Type: Initial release
Revision 1.1Jan 25, 2012Group: Database references
Revision 1.2Apr 9, 2014Group: Source and taxonomy
Revision 1.3Jan 24, 2018Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 1.4Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transcriptional regulatory repressor protein (TETR-family)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,3272
Polymers25,9531
Non-polymers3741
Water543
1
A: Transcriptional regulatory repressor protein (TETR-family)
hetero molecules

A: Transcriptional regulatory repressor protein (TETR-family)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,6554
Polymers51,9062
Non-polymers7492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_554-y,-x,-z-1/21
Buried area2770 Å2
ΔGint-23 kcal/mol
Surface area17050 Å2
MethodPISA
Unit cell
Length a, b, c (Å)120.760, 120.760, 33.570
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein Transcriptional regulatory repressor protein (TETR-family)


Mass: 25953.076 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis (bacteria) / Strain: H37Rv / Gene: ethR, MT3970, RV3855 / Production host: Escherichia coli (E. coli) / References: UniProt: P96222, UniProt: P9WMC1*PLUS
#2: Chemical ChemComp-3SF / 5,5,5-trifluoro-1-{4-[3-(1,3-thiazol-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}pentan-1-one


Mass: 374.381 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H17F3N4O2S
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.36 Å3/Da / Density % sol: 47.83 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.7
Details: The crystallization buffer contained: 1.4 - 1.65M Ammonium Sulfate, 15% Glycerol and 0.1M MES pH6.7. , VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Dec 6, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.31→33.57 Å / Num. all: 11439 / Num. obs: 10878 / % possible obs: 95.09 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 3
Reflection shellResolution: 2.31→2.37 Å / % possible all: 99.7

-
Processing

Software
NameVersionClassification
XDSdata scaling
MOLREPphasing
REFMAC5.5.0109refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1T56

1t56


Resolution: 2.31→32.34 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.881 / SU B: 7.377 / SU ML: 0.181 / Cross valid method: THROUGHOUT / ESU R Free: 0.241 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.2739 547 4.8 %RANDOM
Rwork0.21775 ---
obs0.22043 10878 99.93 %-
all-10886 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 30.623 Å2
Baniso -1Baniso -2Baniso -3
1-0.07 Å20 Å20 Å2
2--0.07 Å20 Å2
3----0.14 Å2
Refinement stepCycle: LAST / Resolution: 2.31→32.34 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1500 0 25 3 1528
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0190.0221558
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.9191.9662125
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9525192
X-RAY DIFFRACTIONr_dihedral_angle_2_deg41.21823.61172
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.63415239
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.721513
X-RAY DIFFRACTIONr_chiral_restr0.1160.2242
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0211197
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.9521.5969
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.73621549
X-RAY DIFFRACTIONr_scbond_it2.8973589
X-RAY DIFFRACTIONr_scangle_it4.5954.5576
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.31→2.37 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.358 38 -
Rwork0.258 788 -
obs--99.88 %

+
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