[English] 日本語
Yorodumi
- PDB-7ctw: Wild-type Plasmodium falciparum dihydrofolate reductase-thymidyla... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ctw
TitleWild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with fragment 820, NADPH, dUMP
ComponentsBifunctional dihydrofolate reductase-thymidylate synthase
KeywordsOXIDOREDUCTASE / Anti-folate / anti-malarial / plasmodium falciparum / dihydrofolate reductase / fragment / ANTIBIOTIC
Function / homology
Function and homology information


thymidylate synthase activity / dTMP biosynthetic process / dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process / methylation / nucleotide binding
Similarity search - Function
Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily / Thymidylate synthase / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. ...Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily / Thymidylate synthase / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase-like domain superfamily
Similarity search - Domain/homology
1-(2-methylsulfanylphenyl)piperazine / Chem-NDP / PHOSPHATE ION / Bifunctional dihydrofolate reductase-thymidylate synthase
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.51 Å
AuthorsVanichtanankul, J. / Vitsupakorn, D.
Funding support Thailand, 1items
OrganizationGrant numberCountry
National Center for Genetic Engineering and Biotechnology (Thailand)P1850116 Thailand
CitationJournal: J Enzyme Inhib Med Chem / Year: 2021
Title: Discovery of new non-pyrimidine scaffolds as Plasmodium falciparum DHFR inhibitors by fragment-based screening.
Authors: Hoarau, M. / Vanichtanankul, J. / Srimongkolpithak, N. / Vitsupakorn, D. / Yuthavong, Y. / Kamchonwongpaisan, S.
History
DepositionAug 20, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 28, 2021Provider: repository / Type: Initial release
Revision 1.1Jul 7, 2021Group: Data collection / Category: pdbx_reflns_twin / Item: _pdbx_reflns_twin.diffrn_id
Revision 1.2Nov 29, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z ..._atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bifunctional dihydrofolate reductase-thymidylate synthase
B: Bifunctional dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)145,4506
Polymers143,6562
Non-polymers1,7944
Water1,17165
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10970 Å2
ΔGint-43 kcal/mol
Surface area45940 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.185, 154.730, 163.816
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Bifunctional dihydrofolate reductase-thymidylate synthase


Mass: 71828.000 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Gene: DHFR-TS, dhfr-ts / Production host: Escherichia coli (E. coli) / References: UniProt: A7UD81
#2: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#3: Chemical ChemComp-GEX / 1-(2-methylsulfanylphenyl)piperazine


Mass: 208.323 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H16N2S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 65 / 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: 2.66 Å3/Da / Density % sol: 53.81 %
Crystal growTemperature: 297 K / Method: microbatch / pH: 5 / Details: 0.1M Na malonate, 12% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SEALED TUBE / Type: BRUKER D8 QUEST / Wavelength: 1.5418 Å
DetectorType: BRUKER PHOTON 100 / Detector: CMOS / Date: Oct 10, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
Reflection twin
TypeCrystal-IDIDOperatorDomain-IDFraction
pseudo-merohedral11H, K, L10.89
pseudo-merohedral21-H, -L, -K20.11
ReflectionResolution: 2.51→24.812 Å / Num. obs: 41512 / % possible obs: 97.8 % / Redundancy: 5.68 % / Rmerge(I) obs: 0.1395 / Net I/σ(I): 11.7
Reflection shellResolution: 2.65→2.75 Å / Rmerge(I) obs: 0.3911 / Num. unique obs: 4275 / % possible all: 91.7

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
PROTEUM PLUSdata reduction
PROTEUM PLUSdata scaling
Cootmodel building
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4DPD

4dpd


Resolution: 2.51→24.812 Å / Cor.coef. Fo:Fc: 0.872 / Cor.coef. Fo:Fc free: 0.768 / Cross valid method: NONE / ESU R: 0.201 / ESU R Free: 0.081
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2947 2043 4.922 %
Rwork0.2205 39468 -
all0.224 --
obs-41511 83.26 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 28.124 Å2
Baniso -1Baniso -2Baniso -3
1--1.455 Å2-0 Å2-0 Å2
2--11.879 Å20 Å2
3----10.424 Å2
Refinement stepCycle: LAST / Resolution: 2.51→24.812 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8797 0 115 65 8977
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0139127
X-RAY DIFFRACTIONr_bond_other_d0.0350.0178293
X-RAY DIFFRACTIONr_angle_refined_deg1.6931.64512345
X-RAY DIFFRACTIONr_angle_other_deg2.3341.57919316
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.62451049
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.77123.74500
X-RAY DIFFRACTIONr_dihedral_angle_3_deg21.702151638
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.5491536
X-RAY DIFFRACTIONr_chiral_restr0.0680.21172
X-RAY DIFFRACTIONr_chiral_restr_other1.4450.21
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.029984
X-RAY DIFFRACTIONr_gen_planes_other0.0090.021930
X-RAY DIFFRACTIONr_nbd_refined0.2140.21960
X-RAY DIFFRACTIONr_symmetry_nbd_other0.2320.28484
X-RAY DIFFRACTIONr_nbtor_refined0.1790.24204
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0760.24058
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1830.2275
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0680.213
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2140.235
X-RAY DIFFRACTIONr_nbd_other0.2730.259
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.240.26
X-RAY DIFFRACTIONr_mcbond_it2.5013.0074220
X-RAY DIFFRACTIONr_mcbond_other2.5013.0074219
X-RAY DIFFRACTIONr_mcangle_it4.2214.495261
X-RAY DIFFRACTIONr_mcangle_other4.224.495262
X-RAY DIFFRACTIONr_scbond_it2.0113.1054907
X-RAY DIFFRACTIONr_scbond_other2.0073.1024905
X-RAY DIFFRACTIONr_scangle_it3.4244.6177084
X-RAY DIFFRACTIONr_scangle_other3.4244.6187085
X-RAY DIFFRACTIONr_lrange_it6.61734.17810175
X-RAY DIFFRACTIONr_lrange_other6.61734.18510175
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.51-2.5750X-RAY DIFFRACTION
2.575-2.645X-RAY DIFFRACTION
2.645-2.7220.3731770.3663267X-RAY DIFFRACTION
2.722-2.8060.3991690.3063136X-RAY DIFFRACTION98.0712
2.806-2.8980.3211730.2642978X-RAY DIFFRACTION97.0733
2.898-2.9990.321650.2362942X-RAY DIFFRACTION98.8232
2.999-3.1130.3041430.2222842X-RAY DIFFRACTION98.0296
3.113-3.240.2631330.2042726X-RAY DIFFRACTION98.2474
3.24-3.3840.2611260.22574X-RAY DIFFRACTION95.9488
3.384-3.5490.3131280.2092512X-RAY DIFFRACTION97.6693
3.549-3.7410.3281220.2172401X-RAY DIFFRACTION96.5557
3.741-3.9670.2721050.212261X-RAY DIFFRACTION98.3375
3.967-4.2410.2721140.1882107X-RAY DIFFRACTION96.86
4.241-4.5810.276970.1761991X-RAY DIFFRACTION96.5772
4.581-5.0180.195880.1751829X-RAY DIFFRACTION96.6717
5.018-5.6090.267870.1951693X-RAY DIFFRACTION97.6948
5.609-6.4760.339700.2231497X-RAY DIFFRACTION98.0601
6.476-7.9280.268620.1941289X-RAY DIFFRACTION97.5451
7.928-11.1990.205560.1761012X-RAY DIFFRACTION97.0909

+
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