› 5h4j

X-ray diffraction
1.8Å resolution

Crystal structure of Human dUTPase in complex with N-[(1R)-1-[3-(Cyclopentyloxy)-phenyl]-ethyl]-3-[(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)methoxy]-1-propanesulfonamide

Released:
DOI: 10.2210/pdb5h4j/pdb
PDB entry 5h4j coloured by chain, front view.
PDB entry 5h4j coloured by chain, side view.
PDB entry 5h4j coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy.
Yano W, Yokogawa T, Wakasa T, Yamamura K, Fujioka A, Yoshisue K, Matsushima E, Miyahara S, Miyakoshi H, Taguchi J, Chong KT, Takao Y, Fukuoka M, Matsuo K
Mol Cancer Ther 17 1683-1693 (2018)
PMID: 29748212

Function and Biology Details

Reaction catalysed: 
dUTP + H(2)O = dUMP + diphosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-152585 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 164 amino acids
Theoretical weight: 17.77 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P33316 (Residues: 94-252; Coverage: 63%)
Gene name: DUT
Sequence domains: dUTPase
Structure domains: Deoxyuridine 5'-Triphosphate Nucleotidohydrolase; Chain A

Ligands and Environments

4 bound ligands:
Ligand FKM 1 x FKM
Ligand ZN 1 x ZN
Ligand IMD 1 x IMD
Ligand DMS 1 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: PHOTON FACTORY BEAMLINE BL-17A
Spacegroup: P213
Unit cell:
a: 89.645Å b: 89.645Å c: 89.645Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.17 0.169 0.173
Expression system: Escherichia coli

Quick links

Citations

4 review citations

Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism.
Tsesmetzis et al. (2018)
3 more