[English] 日本語
Yorodumi
- PDB-5hs3: Human thymidylate synthase complexed with dUMP and 3-amino-2-benz... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5hs3
TitleHuman thymidylate synthase complexed with dUMP and 3-amino-2-benzoyl-4-methylthieno[2,3-b]pyridin-6-ol
ComponentsThymidylate synthase
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / nhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
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 / thymidylate synthase / response to vitamin A / 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 / thymidylate synthase / response to vitamin A / 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 cytokine / response to progesterone / 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 / cytoplasm / cytosol
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-KI3 / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / Thymidylate synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.103 Å
AuthorsChen, D. / Almqvist, H. / Axelsson, H. / Jafari, R. / Mateus, A. / Haraldsson, M. / Larsson, A. / Artursson, P. / Molina, D.M. / Lundback, T. / Nordlund, P.
Funding support Singapore, 1items
OrganizationGrant numberCountry
Nanyang Technological UniversityM060080004.70301200 Singapore
CitationJournal: Nat Commun / Year: 2016
Title: CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil
Authors: Almqvist, H. / Axelsson, H. / Jafari, R. / Chen, D. / Mateus, A. / Haraldsson, M. / Larsson, A. / Molina, D.M. / Artursson, P. / Lundback, T. / Nordlund, P.
History
DepositionJan 25, 2016Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Feb 24, 2016Provider: repository / Type: Initial release
Revision 1.1Mar 30, 2016Group: Database references
Revision 1.2Apr 6, 2016Group: Database references
Revision 1.3Feb 19, 2020Group: Data collection / Derived calculations / Category: diffrn_source / pdbx_struct_oper_list
Item: _diffrn_source.pdbx_synchrotron_site / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Nov 8, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Thymidylate synthase
B: Thymidylate synthase
C: Thymidylate synthase
D: Thymidylate synthase
E: Thymidylate synthase
F: Thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)201,70415
Polymers199,0026
Non-polymers2,7029
Water19811
1
A: Thymidylate synthase
D: Thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,2355
Polymers66,3342
Non-polymers9013
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Thymidylate synthase
F: Thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,2355
Polymers66,3342
Non-polymers9013
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Thymidylate synthase
E: Thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,2355
Polymers66,3342
Non-polymers9013
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)108.202, 108.202, 313.931
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein
Thymidylate synthase / TSase


Mass: 33167.047 Da / Num. of mol.: 6 / Fragment: UNP residues 26-313
Source method: isolated from a genetically manipulated source
Details: Residue 1-25 deleted / Source: (gene. exp.) Homo sapiens (human) / Gene: TYMS, TS / Production host: Escherichia coli (E. coli) / References: UniProt: P04818, thymidylate synthase
#2: Chemical
ChemComp-UMP / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / DUMP


Mass: 308.182 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Formula: C9H13N2O8P
#3: Chemical ChemComp-KI3 / 3-amino-2-benzoyl-4-methylthieno[2,3-b]pyridin-6-ol


Mass: 284.333 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Formula: C15H12N2O2S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 11 / 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: 2.32 Å3/Da / Density % sol: 46.94 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 0.1 M sodium cacodylate, 15% PEG 4000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Sep 17, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 3.1→30 Å / Num. obs: 34749 / % possible obs: 99.9 % / Redundancy: 11.9 % / Net I/σ(I): 15.56

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1HVY

1hvy


Resolution: 3.103→28.106 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 33.81 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2684 1664 4.83 %
Rwork0.1798 --
obs0.1843 34453 99.29 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.103→28.106 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13594 0 180 11 13785
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01414149
X-RAY DIFFRACTIONf_angle_d1.09619201
X-RAY DIFFRACTIONf_dihedral_angle_d20.3715303
X-RAY DIFFRACTIONf_chiral_restr0.062024
X-RAY DIFFRACTIONf_plane_restr0.0052483
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.1029-3.19410.3791610.24312648X-RAY DIFFRACTION99
3.1941-3.2970.30131380.22342689X-RAY DIFFRACTION100
3.297-3.41470.32951240.23252690X-RAY DIFFRACTION100
3.4147-3.55120.31661260.2152707X-RAY DIFFRACTION100
3.5512-3.71240.25421360.19332723X-RAY DIFFRACTION100
3.7124-3.90770.30381280.18332702X-RAY DIFFRACTION100
3.9077-4.15180.25281220.17462744X-RAY DIFFRACTION100
4.1518-4.47120.2271470.15562719X-RAY DIFFRACTION100
4.4712-4.9190.21661430.14832741X-RAY DIFFRACTION99
4.919-5.62580.28041130.17652780X-RAY DIFFRACTION99
5.6258-7.06920.29141700.19022757X-RAY DIFFRACTION99
7.0692-28.1070.24081560.15052889X-RAY DIFFRACTION97

+
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