[English] 日本語
Yorodumi
- PDB-8pf3: Crystal structure of Trypanosoma brucei trypanothione reductase i... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8pf3
TitleCrystal structure of Trypanosoma brucei trypanothione reductase in complex with 1-(3,4-dichlorobenzyl)-4-(((5-((4-fluorophenethyl)carbamoyl)furan-2-yl)methyl)(4-fluorophenyl)carbamoyl)-1-(3-phenylpropyl)piperazin-1-ium
ComponentsTrypanothione reductase
KeywordsOXIDOREDUCTASE / oxidoreductase activity / nucleotide binding / flavoenzyme / inhibitor binding
Function / homology
Function and homology information


trypanothione-disulfide reductase / trypanothione-disulfide reductase (NADPH) activity / cell redox homeostasis / flavin adenine dinucleotide binding / cytoplasm
Similarity search - Function
Trypanothione reductase / : / Pyridine nucleotide-disulphide oxidoreductase, class I / Pyridine nucleotide-disulphide oxidoreductase, class I, active site / Pyridine nucleotide-disulphide oxidoreductases class-I active site. / Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain / Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain / FAD/NAD-linked reductase, dimerisation domain superfamily / FAD/NAD(P)-binding domain / Pyridine nucleotide-disulphide oxidoreductase / FAD/NAD(P)-binding domain superfamily
Similarity search - Domain/homology
FLAVIN-ADENINE DINUCLEOTIDE / IMIDAZOLE / DI(HYDROXYETHYL)ETHER / : / Trypanothione reductase
Similarity search - Component
Biological speciesTrypanosoma brucei (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsExertier, C. / Ilari, A. / Fiorillo, A. / Antonelli, L.
Funding support Italy, 1items
OrganizationGrant numberCountry
Italian Ministry of EducationFISR2019_03796 Italy
CitationJournal: J.Med.Chem. / Year: 2024
Title: Fragment Merging, Growing, and Linking Identify New Trypanothione Reductase Inhibitors for Leishmaniasis.
Authors: Exertier, C. / Salerno, A. / Antonelli, L. / Fiorillo, A. / Ocello, R. / Seghetti, F. / Caciolla, J. / Uliassi, E. / Masetti, M. / Fiorentino, E. / Orsini, S. / Di Muccio, T. / Ilari, A. / Bolognesi, M.L.
History
DepositionJun 15, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 3, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Trypanothione reductase
B: Trypanothione reductase
C: Trypanothione reductase
D: Trypanothione reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)220,61417
Polymers213,9924
Non-polymers6,62313
Water10,719595
1
A: Trypanothione reductase
B: Trypanothione reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)110,3429
Polymers106,9962
Non-polymers3,3467
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10820 Å2
ΔGint-69 kcal/mol
Surface area36950 Å2
2
C: Trypanothione reductase
D: Trypanothione reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)110,2738
Polymers106,9962
Non-polymers3,2776
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area11040 Å2
ΔGint-70 kcal/mol
Surface area37160 Å2
Unit cell
Length a, b, c (Å)100.703, 63.742, 170.096
Angle α, β, γ (deg.)90.00, 97.75, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Trypanothione reductase / N(1) / N(8)-bis(glutathionyl)spermidine reductase


Mass: 53497.969 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Details: Due to high flexibility of protein terminal parts, the electronic density being absent for the N- and C-terminal segment, we were not able to reconstruct the polypeptid chain for the initial ...Details: Due to high flexibility of protein terminal parts, the electronic density being absent for the N- and C-terminal segment, we were not able to reconstruct the polypeptid chain for the initial GS and the last DSNL residues.
Source: (gene. exp.) Trypanosoma brucei (eukaryote) / Gene: DPX39_100110900 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: A0A3L6KZJ1, trypanothione-disulfide reductase

-
Non-polymers , 5 types, 608 molecules

#2: Chemical
ChemComp-FAD / FLAVIN-ADENINE DINUCLEOTIDE / Flavin adenine dinucleotide


Mass: 785.550 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C27H33N9O15P2 / Comment: FAD*YM
#3: Chemical
ChemComp-YJ6 / 4-[(3,4-dichlorophenyl)methyl]-~{N}-(4-fluorophenyl)-~{N}-[[5-[2-(4-fluorophenyl)ethylcarbamoyl]furan-2-yl]methyl]-4-(3-phenylpropyl)-1,4$l^{4}-diazinane-1-carboxamide / -(3,4-Dichlorobenzyl)-4-(((5-((4-fluorophenethyl)carbamoyl)furan-2-yl)methyl)(4-fluorophenyl)carbamoyl)-1-(3-phenylpropyl)piperazin-1-ium


Mass: 746.692 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C41H41Cl2F2N4O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER / Diethylene glycol


Mass: 106.120 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O3
#5: Chemical ChemComp-IMD / IMIDAZOLE / Imidazole


Mass: 69.085 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H5N2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 595 / 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: 2.53 Å3/Da / Density % sol: 51.34 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 13-15% PEG3350, 22-24% MPD, 40 mM imidazole pH 7.5, 50 mM NaBr

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ELETTRA / Beamline: 11.2C / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 31, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→168.54 Å / Num. obs: 117489 / % possible obs: 99.7 % / Redundancy: 6 % / CC1/2: 0.996 / Net I/σ(I): 10.37
Reflection shellResolution: 2.15→2.28 Å / Mean I/σ(I) obs: 2.25 / Num. unique obs: 18906 / CC1/2: 0.741

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→168.54 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.944 / SU B: 5.936 / SU ML: 0.149 / Cross valid method: THROUGHOUT / ESU R: 0.23 / ESU R Free: 0.186 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22408 5804 5 %RANDOM
Rwork0.17902 ---
obs0.1813 111276 99.62 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 42.179 Å2
Baniso -1Baniso -2Baniso -3
1-1.52 Å2-0 Å20.87 Å2
2---0.72 Å20 Å2
3----1 Å2
Refinement stepCycle: 1 / Resolution: 2.15→168.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14846 0 453 595 15894
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.01315909
X-RAY DIFFRACTIONr_bond_other_d0.0040.01515139
X-RAY DIFFRACTIONr_angle_refined_deg1.541.64221657
X-RAY DIFFRACTIONr_angle_other_deg1.271.57734975
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.01952018
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.45722.682716
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.135152624
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.1061575
X-RAY DIFFRACTIONr_chiral_restr0.0720.22073
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0217999
X-RAY DIFFRACTIONr_gen_planes_other0.0020.023483
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_it3.0684.1067892
X-RAY DIFFRACTIONr_mcbond_other3.0654.1057891
X-RAY DIFFRACTIONr_mcangle_it4.4116.1479877
X-RAY DIFFRACTIONr_mcangle_other4.4126.1489878
X-RAY DIFFRACTIONr_scbond_it3.8934.8128017
X-RAY DIFFRACTIONr_scbond_other3.8924.8128018
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.0117.00111750
X-RAY DIFFRACTIONr_long_range_B_refined8.59248.68617094
X-RAY DIFFRACTIONr_long_range_B_other8.59848.65517020
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.15→2.202 Å
RfactorNum. reflection% reflection
Rfree0.315 427 -
Rwork0.258 7908 -
obs--96.22 %

+
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