[English] 日本語
Yorodumi
- PDB-1ju6: Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1ju6
TitleHuman Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate
ComponentsTHYMIDYLATE SYNTHASE
KeywordsTRANSFERASE / antifolate / dTMP synthesis / drug resistance / cancer
Function / homology
Function and homology information


uracil metabolic process / response to organophosphorus / intestinal epithelial cell maturation / response to folic acid / Interconversion of nucleotide di- and triphosphates / response to vitamin A / thymidylate synthase / sequence-specific mRNA binding / cartilage development / tetrahydrofolate interconversion ...uracil metabolic process / response to organophosphorus / intestinal epithelial cell maturation / response to folic acid / Interconversion of nucleotide di- and triphosphates / response to vitamin A / thymidylate synthase / sequence-specific mRNA binding / cartilage development / tetrahydrofolate interconversion / thymidylate synthase activity / folic acid binding / dTMP biosynthetic process / dTTP biosynthetic process / DNA biosynthetic process / G1/S-Specific Transcription / developmental growth / dihydrofolate reductase activity / response to glucocorticoid / mRNA regulatory element binding translation repressor activity / response to progesterone / response to cytokine / liver regeneration / response to toxic substance / circadian rhythm / methylation / response to ethanol / mitochondrial inner membrane / negative regulation of translation / mitochondrial matrix / response to xenobiotic stimulus / protein homodimerization activity / mitochondrion / nucleus / cytosol / cytoplasm
Similarity search - Function
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 / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-LYA / PHOSPHATE ION / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / Thymidylate synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.89 Å
AuthorsSayre, P.H. / Finer-Moore, J.S. / Fritz, T.A. / Biermann, D. / Gates, S.B. / MacKellar, W.C. / Patel, V.F. / Stroud, R.M.
Citation
Journal: J.Mol.Biol. / Year: 2001
Title: Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases.
Authors: Sayre, P.H. / Finer-Moore, J.S. / Fritz, T.A. / Biermann, D. / Gates, S.B. / MacKellar, W.C. / Patel, V.F. / Stroud, R.M.
#1: Journal: Biochemistry / Year: 1995
Title: Crystal Structure of Human Thymidylate Synthase: A Structural Mechanism for Guiding Substrates into the Active Site
Authors: Schiffer, C.A. / Clifton, I.J. / Davisson, V.J. / Santi, D.V. / Stroud, R.M.
History
DepositionAug 23, 2001Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 19, 2001Provider: repository / Type: Initial release
Revision 1.1Apr 27, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 27, 2021Group: Database references / Derived calculations
Category: database_2 / struct_conn ...database_2 / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: THYMIDYLATE SYNTHASE
B: THYMIDYLATE SYNTHASE
C: THYMIDYLATE SYNTHASE
D: THYMIDYLATE SYNTHASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)145,97713
Polymers142,9394
Non-polymers3,0379
Water86548
1
A: THYMIDYLATE SYNTHASE
B: THYMIDYLATE SYNTHASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,0367
Polymers71,4702
Non-polymers1,5665
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7880 Å2
ΔGint-33 kcal/mol
Surface area20890 Å2
MethodPISA
2
C: THYMIDYLATE SYNTHASE
D: THYMIDYLATE SYNTHASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,9416
Polymers71,4702
Non-polymers1,4714
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7610 Å2
ΔGint-28 kcal/mol
Surface area20910 Å2
MethodPISA
Unit cell
Length a, b, c (Å)68.138, 69.633, 73.958
Angle α, β, γ (deg.)71.67, 85.72, 75.11
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
THYMIDYLATE SYNTHASE / / TS


Mass: 35734.859 Da / Num. of mol.: 4 / Mutation: R46E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pGCHTS-TAA / Production host: Escherichia coli (E. coli) / Strain (production host): DH5a / References: UniProt: P04818, thymidylate synthase
#2: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#3: Chemical
ChemComp-UMP / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / DUMP / Deoxyuridine monophosphate


Mass: 308.182 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C9H13N2O8P
#4: Chemical
ChemComp-LYA / 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC ACID / LY231514 / Pemetrexed


Mass: 427.411 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C20H21N5O6 / Comment: medication, chemotherapy*YM
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 48 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 2

-
Sample preparation

CrystalDensity Matthews: 2.25 Å3/Da / Density % sol: 45.35 %
Crystal growTemperature: 296 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: PEG-monomethyl ether 5000, sodium cacodylate, ammonium sulfate, KCL, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 296K

-
Data collection

Diffraction
IDMean temperature (K)Crystal-ID
1103.21
2103.21
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.54178 Å
Detector
TypeIDDetectorDate
RIGAKU RAXIS IV1IMAGE PLATESep 1, 1997
RIGAKU RAXIS IV2IMAGE PLATESep 2, 1997
Radiation
IDMonochromatorProtocolMonochromatic (M) / Laue (L)Scattering typeWavelength-ID
1graphiteSINGLE WAVELENGTHMx-ray1
2graphiteSINGLE WAVELENGTHMx-ray1
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 2.8→23 Å / Num. all: 24659 / Num. obs: 24659 / % possible obs: 88 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 1.9 % / Biso Wilson estimate: 41.9 Å2 / Rmerge(I) obs: 0.138 / Net I/σ(I): 7.4
Reflection shellResolution: 2.8→2.88 Å / Rmerge(I) obs: 0.333 / Mean I/σ(I) obs: 2 / % possible all: 74

-
Processing

Software
NameClassification
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: thymidylate synthase portion of the Leishmania major DHFR-TS bifunctional enzyme

Resolution: 2.89→22.95 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 173248.96 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
Details: Residues 1 through 27 in each chain are disordered and were not included in refinement. All four monomers in the asymmetric unit were initially constrained to have equivalent structures. NCS ...Details: Residues 1 through 27 in each chain are disordered and were not included in refinement. All four monomers in the asymmetric unit were initially constrained to have equivalent structures. NCS constraints were relaxed to restraints in the final cycles of refinement.
RfactorNum. reflection% reflectionSelection details
Rfree0.264 2315 9.9 %RANDOM
Rwork0.236 ---
obs0.239 23376 83.8 %-
all-23376 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 33.305 Å2 / ksol: 0.361834 e/Å3
Displacement parametersBiso mean: 23.8 Å2
Baniso -1Baniso -2Baniso -3
1-1.65 Å2-1.99 Å26.33 Å2
2---4.36 Å2-1.09 Å2
3---2.71 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.43 Å0.39 Å
Luzzati d res low-5 Å
Luzzati sigma a0.51 Å0.52 Å
Refinement stepCycle: LAST / Resolution: 2.89→22.95 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9236 0 209 48 9493
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_angle_deg1.5
X-RAY DIFFRACTIONc_dihedral_angle_d23.3
X-RAY DIFFRACTIONc_improper_angle_d0.83
Refine LS restraints NCSNCS model details: CONSTR
LS refinement shellResolution: 2.89→3.07 Å / Rfactor Rfree error: 0.018 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.316 323 10.3 %
Rwork0.324 2826 -
obs--67.7 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN.TOP
X-RAY DIFFRACTION2WATER_REP.PARAMWATER.TOP
X-RAY DIFFRACTION3LY231514.PARLY231514.TOP
X-RAY DIFFRACTION4PARAMED.LIGTOPO_COVALENT.DUMP
X-RAY DIFFRACTION5ION.PARAM

+
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