[English] 日本語
Yorodumi
- PDB-4qjc: Human dihydrofolate reductase ternary complex with NADPH and inhi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4qjc
TitleHuman dihydrofolate reductase ternary complex with NADPH and inhibitor 26 (N~6~-METHYL-N~6~-(3,4,5-TRIFLUOROPHENYL)PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE)
ComponentsDihydrofolate reductase
Keywordsoxidoreductase/oxidoreductase inhibitor / dihydrofolate reductase / inhibitor binding / Rossman fold / hydrolase / cofactor / oxidoreductase-oxidoreductase inhibitor complex
Function / homology
Function and homology information


regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / sequence-specific mRNA binding / response to methotrexate / axon regeneration / folic acid binding / G1/S-Specific Transcription / dihydrofolate metabolic process ...regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / sequence-specific mRNA binding / response to methotrexate / axon regeneration / folic acid binding / G1/S-Specific Transcription / dihydrofolate metabolic process / glycine biosynthetic process / dihydrofolate reductase / dihydrofolate reductase activity / folic acid metabolic process / NADPH binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / tetrahydrofolate biosynthetic process / mRNA regulatory element binding translation repressor activity / positive regulation of nitric-oxide synthase activity / one-carbon metabolic process / NADP binding / negative regulation of translation / mRNA binding / mitochondrion / cytosol
Similarity search - Function
Dihydrofolate Reductase, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase-like domain superfamily / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-IXE / Chem-NDP / Dihydrofolate reductase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.62 Å
AuthorsCody, V.
CitationJournal: Acta Crystallogr F Struct Biol Commun / Year: 2015
Title: Structure-activity correlations for three pyrido[2,3-d]pyrimidine antifolates binding to human and Pneumocystis carinii dihydrofolate reductase.
Authors: Cody, V. / Pace, J. / Namjoshi, O.A. / Gangjee, A.
History
DepositionJun 3, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2015Provider: repository / Type: Initial release
Revision 1.1Jul 1, 2015Group: Database references
Revision 1.2Nov 22, 2017Group: Refinement description / Category: software
Revision 1.3Sep 20, 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: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,4153
Polymers21,3501
Non-polymers1,0662
Water1,892105
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)84.486, 84.486, 77.872
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

#1: Protein Dihydrofolate reductase


Mass: 21349.525 Da / Num. of mol.: 1 / Fragment: human dihydrofolate reductase
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DHFR / Plasmid: pET-SUMO-hDHFR / Production host: Escherichia coli (E. coli) / Strain (production host): pDS5(DE3) / References: UniProt: P00374, dihydrofolate reductase
#2: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#3: Chemical ChemComp-IXE / N~6~-methyl-N~6~-(3,4,5-trifluorophenyl)pyrido[2,3-d]pyrimidine-2,4,6-triamine


Mass: 320.273 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H11F3N6
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 105 / 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: 2.51 Å3/Da / Density % sol: 50.9 %
Crystal growTemperature: 287 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 30% AmSO4, 3% v/v ETOH, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 287K

-
Data collection

DiffractionMean temperature: 113 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.975 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Jun 2, 2013 / Details: mirrors
RadiationMonochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.975 Å / Relative weight: 1
ReflectionResolution: 1.53→34.4 Å / Num. obs: 29910 / % possible obs: 96.3 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 3.3 % / Biso Wilson estimate: 27.9 Å2 / Rmerge(I) obs: 0.062 / Rsym value: 0.039 / Net I/σ(I): 10.2
Reflection shellResolution: 1.54→1.62 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.75 / Mean I/σ(I) obs: 1.2 / Num. unique all: 3757 / Rsym value: 0.92 / % possible all: 83

-
Processing

Software
NameVersionClassification
XDSdata scaling
MOLREPphasing
REFMAC5.6.0117refinement
XDSdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1u72

1u72


Resolution: 1.62→34.37 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.955 / SU B: 1.932 / SU ML: 0.066 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 2 / ESU R: 0.093 / ESU R Free: 0.094 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.2177 1319 5.1 %RANDOM
Rwork0.18328 ---
all0.206 ---
obs0.18502 24614 98.52 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 23.247 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error free: 0.205 Å
Refinement stepCycle: LAST / Resolution: 1.62→34.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1502 0 71 105 1678
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0260.021614
X-RAY DIFFRACTIONr_angle_refined_deg2.5242.0352192
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8325185
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.5324.78971
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.74415286
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.707158
X-RAY DIFFRACTIONr_chiral_restr0.1840.2233
X-RAY DIFFRACTIONr_gen_planes_refined0.0150.0211209
LS refinement shellResolution: 1.62→1.662 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.337 105 -
Rwork0.278 1808 -
obs-3757 83 %

+
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://pdbjlvh1.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