[English] 日本語
Yorodumi
- PDB-3iro: Trypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3iro
TitleTrypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase complexed with NADPH and Q-8 antifolate
ComponentsBifunctional dihydrofolate reductase-thymidylate synthase
KeywordsOXIDOREDUCTASE / TRANSFERASE / Trypanosoma cruzi / DHFR-TS antifolate complex / Methyltransferase / Multifunctional enzyme / NADP / Nucleotide biosynthesis / One-carbon metabolism
Function / homology
Function and homology information


thymidylate synthase / thymidylate synthase activity / dTMP biosynthetic process / dihydrofolate reductase / dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process / methylation
Similarity search - Function
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 ...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. / Dihydrofolate reductase-like domain superfamily / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-2CY / ACETATE ION / Chem-NDP / PHOSPHATE ION / Bifunctional dihydrofolate reductase-thymidylate synthase
Similarity search - Component
Biological speciesTrypanosoma cruzi (eukaryote)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsChitnumsub, P. / Yuvaniyama, J. / Yuthavong, Y.
CitationJournal: To be Published
Title: Structural basis of antifolate inhibition of Trypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase
Authors: Chitnumsub, P. / Yuvaniyama, J. / Vilaivan, T. / Vanichtanankul, J. / Kamchonwongpaisan, S. / Yuthavong, Y.
History
DepositionAug 24, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 28, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version
Revision 1.3Apr 4, 2018Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.4Sep 6, 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
C: Bifunctional dihydrofolate reductase-thymidylate synthase
D: Bifunctional dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)241,16228
Polymers235,7124
Non-polymers5,45024
Water1,49583
1
A: Bifunctional dihydrofolate reductase-thymidylate synthase
B: Bifunctional dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)120,52213
Polymers117,8562
Non-polymers2,66611
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7960 Å2
ΔGint-43 kcal/mol
Surface area42660 Å2
MethodPISA
2
C: Bifunctional dihydrofolate reductase-thymidylate synthase
D: Bifunctional dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)120,64015
Polymers117,8562
Non-polymers2,78413
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8390 Å2
ΔGint-44 kcal/mol
Surface area42390 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.544, 165.936, 84.718
Angle α, β, γ (deg.)90.000, 113.410, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Bifunctional dihydrofolate reductase-thymidylate synthase / DHFR-TS / Dihydrofolate reductase / Thymidylate synthase


Mass: 58928.121 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Trypanosoma cruzi (eukaryote) / Strain: Y / Plasmid: pET11c / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) pLysS
References: UniProt: Q27793, dihydrofolate reductase, thymidylate synthase

-
Non-polymers , 6 types, 107 molecules

#2: Chemical
ChemComp-2CY / 5-[3-(3-fluorophenoxy)propoxy]quinazoline-2,4-diamine


Mass: 328.341 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C17H17FN4O2
#3: Chemical
ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate


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


Mass: 94.971 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: PO4
#5: Chemical
ChemComp-ACT / ACETATE ION / Acetate


Mass: 59.044 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C2H3O2
#6: 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
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 83 / 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: 2.23 Å3/Da / Density % sol: 44.88 %
Crystal growTemperature: 297 K / Method: microbatch / pH: 5.6
Details: PEG4000, NH4OAc, pH 5.6, microbatch, temperature 297K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: ENRAF-NONIUS FR591 / Wavelength: 1.54 Å
DetectorType: Kappa CCD / Detector: CCD / Date: Aug 30, 2005
RadiationMonochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.8→45.07 Å / Num. all: 48261 / Num. obs: 48286 / % possible obs: 95.1 % / Observed criterion σ(F): 0 / Biso Wilson estimate: 48 Å2 / Limit h max: 26 / Limit h min: -29 / Limit k max: 59 / Limit k min: -29 / Limit l max: 30 / Limit l min: 0 / Observed criterion F max: 1995264.21 / Observed criterion F min: 25.4 / Rsym value: 0.097 / Χ2: 1.472 / Net I/σ(I): 9.7
Reflection shellResolution: 2.8→2.9 Å / Num. unique all: 4296 / Rsym value: 0.397 / Χ2: 1.264 / % possible all: 85

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
CNS1.2refinement
PDB_EXTRACT3.005data extraction
HKL-2000data collection
HKL-2000data reduction
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: A partial refined structure of 1IRM

1irm


Resolution: 2.8→45.07 Å / Rfactor Rfree error: 0.006 / Occupancy max: 1 / Occupancy min: 1 / Isotropic thermal model: Overall / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.277 2478 5.1 %random
Rwork0.206 ---
all-50769 --
obs-48261 95.1 %-
Solvent computationSolvent model: CNS bulk solvent model used / Bsol: 23.5073 Å2 / ksol: 0.35 e/Å3
Displacement parametersBiso max: 90.76 Å2 / Biso mean: 32.37 Å2 / Biso min: 1.76 Å2
Baniso -1Baniso -2Baniso -3
1--0.98 Å20 Å21.38 Å2
2--0.67 Å20 Å2
3---0.32 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.44 Å0.32 Å
Luzzati d res low-5 Å
Luzzati sigma a0.64 Å0.48 Å
Luzzati d res high-2.8
Refinement stepCycle: LAST / Resolution: 2.8→45.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms16419 0 360 83 16862
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.007
X-RAY DIFFRACTIONx_angle_deg1.4
X-RAY DIFFRACTIONx_torsion_deg23.4
X-RAY DIFFRACTIONx_torsion_impr_deg0.88
LS refinement shell

Refine-ID: X-RAY DIFFRACTION

Resolution (Å)Rfactor RfreeNum. reflection Rfree% reflection Rfree (%)Rfactor RworkNum. reflection RworkRfactor Rfree errorNum. reflection allNum. reflection obs% reflection obs (%)
2.8-2.930.372624.90.32851210.0236338538384.9
2.93-3.080.3643075.40.29353960.0216325570390.2
3.08-3.280.33929750.25856670.026335596494.1
3.28-3.530.3123175.20.23358180.0186348613596.6
3.53-3.880.2530850.19559100.0146325621898.3
3.88-4.440.2443305.30.16759540.0136334628499.2
4.44-5.60.2343275.20.15759700.0136365629798.9
5.6-45.070.2453305.30.17459470.0136427627797.7

+
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