› 1sej

X-ray diffraction
2.87Å resolution

Crystal Structure of Dihydrofolate Reductase-Thymidylate Synthase from Cryptosporidium hominis Bound to 1843U89/NADPH/dUMP

Released:
DOI: 10.2210/pdb1sej/pdb
PDB entry 1sej coloured by chain, front view.
PDB entry 1sej coloured by chain, side view.
PDB entry 1sej coloured by chain, top view.
Source organism: Cryptosporidium hominis
Primary publication:
Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance.
Anderson AC
Acta Crystallogr Sect F Struct Biol Cryst Commun 61 258-62 (2005)
PMID: 16511011

Function and Biology Details

Reactions catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Biochemical function:
Biological process:
Cellular component:
Sequence domains:
Structure domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-173272 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional dihydrofolate reductase-thymidylate synthase Chains: A, B, C, D, E
Molecule details ›
Chains: A, B, C, D, E
Length: 521 amino acids
Theoretical weight: 60.26 KDa
Source organism: Cryptosporidium hominis
Expression system: Escherichia coli
UniProt:
  • Canonical: Q27552 (Residues: 1-521; Coverage: 100%)
Gene name: DHFR-TS
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NDP 5 x NDP
2 bound ligands:
Ligand UMP 5 x UMP
Ligand F89 10 x F89
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL7-1
Spacegroup: C2
Unit cell:
a: 214.9Å b: 116.3Å c: 219.7Å
α: 90° β: 95.23° γ: 90°
R-values:
R R work R free
0.22 0.22 0.237
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Post-genomics resources and tools for studying apicomplexan metabolism.
Hung et al. (2011)
2 more

3 mentions without citation

Structure-based approach to the development of potent and selective inhibitors of dihydrofolate reductase from cryptosporidium.
Bolstad et al. (2008)
2 more