› 3nu0

X-ray diffraction
1.35Å resolution

Design, Synthesis, Biological Evaluation and X-ray Crystal Structure of Novel Classical 6,5,6-TricyclicBenzo[4,5]thieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors

Released:
DOI: 10.2210/pdb3nu0/pdb
PDB entry 3nu0 coloured by chain, front view.
PDB entry 3nu0 coloured by chain, side view.
PDB entry 3nu0 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.
Zhang X, Zhou X, Kisliuk RL, Piraino J, Cody V, Gangjee A
Bioorg Med Chem 19 3585-94 (2011)
PMID: 21550809

Function and Biology Details

Reaction catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132447 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chain: A
Molecule details ›
Chain: A
Length: 186 amino acids
Theoretical weight: 21.35 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00374 (Residues: 2-187; Coverage: 100%)
Gene name: DHFR
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments


Cofactor: Ligand NDP 1 x NDP
2 bound ligands:
Ligand 3TU 1 x 3TU
Ligand SO4 3 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL9-2
Spacegroup: R3
Unit cell:
a: 84.395Å b: 84.395Å c: 78.193Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.212 0.18 0.209
Expression system: Escherichia coli

Quick links

Citations

10 citation in other articles

An innovative strategy for dual inhibitor design and its application in dual inhibition of human thymidylate synthase and dihydrofolate reductase enzymes.
Arooj et al. (2013)
9 more

3 mentions without citation

5-(Thiophen-2-yl)-1,3,4-thiadiazole derivatives: synthesis, molecular docking and in vitro cytotoxicity evaluation as potential anticancer agents.
Gomha et al. (2018)
2 more