[English] 日本語
Yorodumi
- PDB-4dph: Quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum di... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4dph
TitleQuadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with P65 and NADPH
ComponentsBifunctional dihydrofolate reductase-thymidylate synthase
KeywordsOXIDOREDUCTASE / TRANSFERASE / Plasmodium falciparum / antifolate / Rossmann fold / Reductase / NADPH binding
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 / mitochondrion / cytosol
Similarity search - Function
Single alpha-helices involved in coiled-coils or other helix-helix interfaces - #2210 / Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate Synthase; Chain A / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily ...Single alpha-helices involved in coiled-coils or other helix-helix interfaces - #2210 / Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate Synthase; Chain A / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily / Thymidylate synthase / Dihydrofolate Reductase, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase domain / Dihydrofolate reductase / Single alpha-helices involved in coiled-coils or other helix-helix interfaces / Dihydrofolate reductase-like domain superfamily / Helix non-globular / Special / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
BETA-MERCAPTOETHANOL / Chem-NDP / Chem-P65 / PHOSPHATE ION / Bifunctional dihydrofolate reductase-thymidylate synthase
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2.38 Å
AuthorsYuthavong, Y. / Vilaivan, T. / Kamchonwongpaisan, S. / Charman, S.A. / McLennan, D.N. / White, K.L. / Vivas, L. / Bongard, E. / Chitnumsub, P. / Tarnchompoo, B. ...Yuthavong, Y. / Vilaivan, T. / Kamchonwongpaisan, S. / Charman, S.A. / McLennan, D.N. / White, K.L. / Vivas, L. / Bongard, E. / Chitnumsub, P. / Tarnchompoo, B. / Thongphanchang, C. / Taweechai, S. / Vanichtanakul, J. / Arwon, U. / Fantauzzi, P. / Yuvaniyama, J. / Charman, W.N. / Matthews, D.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2012
Title: Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target
Authors: Yuthavong, Y. / Tarnchompoo, B. / Vilaivan, T. / Chitnumsub, P. / Kamchonwongpaisan, S. / Charman, S.A. / McLennan, D.N. / White, K.L. / Vivas, L. / Bongard, E. / Thongphanchang, C. / ...Authors: Yuthavong, Y. / Tarnchompoo, B. / Vilaivan, T. / Chitnumsub, P. / Kamchonwongpaisan, S. / Charman, S.A. / McLennan, D.N. / White, K.L. / Vivas, L. / Bongard, E. / Thongphanchang, C. / Taweechai, S. / Vanichtanankul, J. / Rattanajak, R. / Arwon, U. / Fantauzzi, P. / Yuvaniyama, J. / Charman, W.N. / Matthews, D.
History
DepositionFeb 13, 2012Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Nov 14, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 8, 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_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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: Bifunctional dihydrofolate reductase-thymidylate synthase
B: Bifunctional dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)146,56512
Polymers143,8162
Non-polymers2,74910
Water7,891438
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area11600 Å2
ΔGint-53 kcal/mol
Surface area46910 Å2
MethodPISA
Unit cell
Length a, b, c (Å)57.951, 156.447, 164.653
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Bifunctional dihydrofolate reductase-thymidylate synthase


Mass: 71908.133 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Strain: V1/S / Gene: DHFR-TS / Plasmid: pET17b / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: D9N170, dihydrofolate reductase, thymidylate synthase

-
Non-polymers , 5 types, 448 molecules

#2: Chemical ChemComp-P65 / 2,4-diamino-6-methyl-5-[3-(2,4,5-trichlorophenoxy)propyloxy]pyrimidine


Mass: 377.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H15Cl3N4O2
#3: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#4: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#5: Chemical
ChemComp-BME / BETA-MERCAPTOETHANOL


Mass: 78.133 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6OS
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 438 / Source method: isolated from a natural source / Formula: H2O

-
Details

Sequence details1. THE QUADRUPLE MUTATIONS (N51I, C59R, S108N, I164L) OF DHFR-TS IS FOUND IN PLASMODIUM FALCIPARUM ...1. THE QUADRUPLE MUTATIONS (N51I, C59R, S108N, I164L) OF DHFR-TS IS FOUND IN PLASMODIUM FALCIPARUM STRAIN V1/S. 2. THE ENTIRE PROTEIN (REDUCTASE DOMAIN: RESIDUES 1-231; SYNTHASE DOMAIN: RESIDUES 283-608) WAS EXPRESSED IN ONE POLYPEPTIDE CHAIN. SINCE THE DENSITY OF THE JUNCTION PEPTIDES (RESIDUES 232-282) BETWEEN THE TWO DOMAINS ARE NOT VISIBLE FOR BOTH MONOMERS, THERE IS STILL AMBIGUITY REGARDING HOW THE TWO DOMAINS ARE PHYSIOLOGICALLY CONNECTED, HENCE A(1-231)-A(283-608) AND B(1-231)-B(283-608), OR ANOTHER CASE, A(1-231)-B(283-608) AND B(1-231)-A(283-608).

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.59 Å3/Da / Density % sol: 52.6 % / Mosaicity: 0.49 °
Crystal growTemperature: 297 K / Method: microbatch / pH: 4.5
Details: PEG4000, NH4OAc, pH 4.5, Microbatch, temperature 297K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: Cu FINE FOCUS / Wavelength: 1.54 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Dec 22, 2004 / Details: mirrors
RadiationMonochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.38→56.71 Å / Num. obs: 60551 / % possible obs: 95.8 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 1.73 % / Biso Wilson estimate: 49.8 Å2 / Rmerge(I) obs: 0.055 / Χ2: 1.35 / Net I/σ(I): 6.9 / Scaling rejects: 1453
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allΧ2Rejects% possible all
2.38-2.471.710.2921653596851.02883.3
2.47-2.561.720.2622.319263111931.08996.5
2.56-2.681.720.2252.719374112231.231596.8
2.68-2.821.720.1823.219451112671.373797
2.82-31.730.1523.919627113021.514497.2
3-3.231.740.1165.119690112991.677797.4
3.23-3.561.730.0747.619603112371.7212297.3
3.56-4.071.740.04910.719806113321.5912297.7
4.07-5.131.730.0314.619965113291.3136397.7
5.13-56.711.730.02216.420068112170.9265696.7

-
Processing

Software
NameVersionClassificationNB
d*TREK7.1SSIdata scaling
d*TREK7.1SSIdata reduction
REFMAC5.5.0109refinement
PDB_EXTRACT3.1data extraction
CrystalCleardata collection
CNSphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1J3K

1j3k


Resolution: 2.38→54.66 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.905 / Occupancy max: 1 / Occupancy min: 1 / SU B: 9.275 / SU ML: 0.215 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.372 / ESU R Free: 0.283 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2864 3072 5.1 %RANDOM
Rwork0.2189 ---
obs0.2222 60475 99.08 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 120 Å2 / Biso mean: 48.8601 Å2 / Biso min: 20 Å2
Baniso -1Baniso -2Baniso -3
1-2.54 Å20 Å20 Å2
2---1.18 Å20 Å2
3----1.36 Å2
Refinement stepCycle: LAST / Resolution: 2.38→54.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8867 0 168 438 9473
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0229268
X-RAY DIFFRACTIONr_angle_refined_deg1.4891.97312530
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.74751057
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.07424.732467
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.739151643
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.6231538
X-RAY DIFFRACTIONr_chiral_restr0.0980.21339
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0216986
X-RAY DIFFRACTIONr_mcbond_it0.8631.55321
X-RAY DIFFRACTIONr_mcangle_it1.60128663
X-RAY DIFFRACTIONr_scbond_it1.83533947
X-RAY DIFFRACTIONr_scangle_it3.0014.53867
LS refinement shellResolution: 2.38→2.442 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.367 215 -
Rwork0.335 3852 -
all-4067 -
obs--91.11 %

+
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