[English] 日本語
Yorodumi
- PDB-6kpr: Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum di... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6kpr
TitleQuadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with B12155 inhibitor
ComponentsBifunctional dihydrofolate reductase-thymidylate synthase
KeywordsOXIDOREDUCTASE / TRANSFERASE / Dihydrofolate reductase / plasmodium falciparum / Antimalarial / Antifolate / 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
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/dCMP hydroxymethylase / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / 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/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, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase (DHFR) domain profile. / 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
Chem-DQF / Chem-NDP / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / Bifunctional dihydrofolate reductase-thymidylate synthase
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsVanichtanankul, J. / Vitsupakorn, D.
Funding support Thailand, 2items
OrganizationGrant numberCountry
National Center for Genetic Engineering and Biotechnology (Thailand)P1450883 Thailand
National Center for Genetic Engineering and Biotechnology (Thailand)P1850116 Thailand
CitationJournal: Bioorg.Med.Chem. / Year: 2019
Title: 6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.
Authors: Saepua, S. / Sadorn, K. / Vanichtanankul, J. / Anukunwithaya, T. / Rattanajak, R. / Vitsupakorn, D. / Kamchonwongpaisan, S. / Yuthavong, Y. / Thongpanchang, C.
History
DepositionAug 15, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Nov 22, 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)147,02210
Polymers143,8162
Non-polymers3,2058
Water5,981332
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area12450 Å2
ΔGint-54 kcal/mol
Surface area45120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)57.902, 156.504, 165.484
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 / Mutation: N51I, C59R, S108N, I164L
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Gene: DHFR-TS, V1/S / Production host: Escherichia coli (E. coli) / References: UniProt: D9N170

-
Non-polymers , 5 types, 340 molecules

#2: Chemical ChemComp-UMP / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / DUMP / Deoxyuridine monophosphate


Mass: 308.182 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H13N2O8P
#3: 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
#4: Chemical ChemComp-DQF / 4-[3-[3-[2,6-bis(azanyl)-5-(3-chlorophenyl)pyrimidin-4-yl]propoxy]phenoxy]butanoic acid


Mass: 456.922 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H25ClN4O4 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 332 / 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: 2.61 Å3/Da / Density % sol: 52.82 %
Crystal growTemperature: 298 K / Method: microbatch / Details: NaOAc, NH2OAc, PEG 4000

-
Data collection

DiffractionMean temperature: 123 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: BL13B1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 14, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. obs: 88221 / % possible obs: 99.1 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.056 / Rpim(I) all: 0.024 / Rrim(I) all: 0.061 / Χ2: 0.949 / Net I/σ(I): 14.4 / Num. measured all: 549882
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.1-2.1860.44984560.9310.1930.490.84196.5
2.18-2.266.10.34185800.9620.1460.3720.88197.5
2.26-2.376.10.25686680.9750.110.2790.90198.7
2.37-2.496.10.19787710.9840.0850.2150.92599.4
2.49-2.656.30.14888190.990.0630.1610.96299.7
2.65-2.856.40.10588280.9950.0450.1151.02199.9
2.85-3.146.50.07388710.9970.0310.081.01999.8
3.14-3.596.50.05489420.9980.0230.0581.11100
3.59-4.526.30.04589960.9980.020.051.00799.9
4.52-506.20.02792900.9990.0120.0290.79999.2

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
REFMAC5.8.0253refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4dp3

4dp3


Resolution: 2.1→26.988 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.919 / SU B: 4.422 / SU ML: 0.118 / Cross valid method: NONE / ESU R: 0.193 / ESU R Free: 0.176
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2411 4377 5.053 %
Rwork0.195 --
all0.197 --
obs-86619 97.16 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 34.067 Å2
Baniso -1Baniso -2Baniso -3
1--0.021 Å20 Å20 Å2
2--0.129 Å2-0 Å2
3----0.108 Å2
Refinement stepCycle: LAST / Resolution: 2.1→26.988 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8894 0 212 332 9438
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0139324
X-RAY DIFFRACTIONr_bond_other_d0.0030.0178448
X-RAY DIFFRACTIONr_angle_refined_deg1.7151.66912610
X-RAY DIFFRACTIONr_angle_other_deg1.3841.59719669
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.29751058
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.48523.686510
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.434151654
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.1271538
X-RAY DIFFRACTIONr_chiral_restr0.0860.21191
X-RAY DIFFRACTIONr_chiral_restr_other2.0620.218
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0210118
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021976
X-RAY DIFFRACTIONr_nbd_refined0.210.21808
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1820.28324
X-RAY DIFFRACTIONr_nbtor_refined0.1770.24457
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0790.24373
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1560.2427
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0820.23
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1770.231
X-RAY DIFFRACTIONr_nbd_other0.2610.252
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1560.27
X-RAY DIFFRACTIONr_mcbond_it3.273.4194262
X-RAY DIFFRACTIONr_mcbond_other3.273.4194261
X-RAY DIFFRACTIONr_mcangle_it4.9465.0925310
X-RAY DIFFRACTIONr_mcangle_other4.9455.0935311
X-RAY DIFFRACTIONr_scbond_it3.5283.835062
X-RAY DIFFRACTIONr_scbond_other3.5283.8295063
X-RAY DIFFRACTIONr_scangle_it5.4325.5827300
X-RAY DIFFRACTIONr_scangle_other5.4325.5827301
X-RAY DIFFRACTIONr_lrange_it7.89438.83410534
X-RAY DIFFRACTIONr_lrange_other7.938.82210485
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.097-2.1510.2982730.2575098X-RAY DIFFRACTION82.1756
2.151-2.210.2732980.2365528X-RAY DIFFRACTION92.3589
2.21-2.2740.2783300.235495X-RAY DIFFRACTION94.3473
2.274-2.3440.2472820.2235538X-RAY DIFFRACTION96.8386
2.344-2.4210.2483140.2115450X-RAY DIFFRACTION98.6648
2.421-2.5060.2762550.2085331X-RAY DIFFRACTION99.3067
2.506-2.60.2572680.215125X-RAY DIFFRACTION99.7042
2.6-2.7070.2422690.2014980X-RAY DIFFRACTION99.7529
2.707-2.8270.272540.2124784X-RAY DIFFRACTION99.8811
2.827-2.9650.2572340.1974572X-RAY DIFFRACTION99.6475
2.965-3.1250.2692370.2184342X-RAY DIFFRACTION99.6084
3.125-3.3140.2562230.2044138X-RAY DIFFRACTION99.6572
3.314-3.5430.2581760.23907X-RAY DIFFRACTION99.8045
3.543-3.8270.2252090.1893628X-RAY DIFFRACTION99.8439
3.827-4.1910.2131720.1723366X-RAY DIFFRACTION99.6901
4.191-4.6850.1861730.1463035X-RAY DIFFRACTION99.7202
4.685-5.4090.191320.1532724X-RAY DIFFRACTION99.3046
5.409-6.620.2411300.1822317X-RAY DIFFRACTION100
6.62-9.3470.212960.1611850X-RAY DIFFRACTION100
9.347-26.9880.238520.1981034X-RAY DIFFRACTION94.3527

+
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