› 4xec

X-ray diffraction
2.69Å resolution

Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ETHYL-5-[(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)PHENYL]BUT-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1061)

Released:
DOI: 10.2210/pdb4xec/pdb
PDB entry 4xec coloured by chain, front view.
PDB entry 4xec coloured by chain, side view.
PDB entry 4xec coloured by chain, top view.
Source organism: Staphylococcus aureus
Primary publication:
Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.
Keshipeddy S, Reeve SM, Anderson AC, Wright DL
J Am Chem Soc 137 8983-90 (2015)
PMID: 26098608

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-140887 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chain: X
Molecule details ›
Chain: X
Length: 157 amino acids
Theoretical weight: 18.02 KDa
Source organism: Staphylococcus aureus
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P0A017 (Residues: 2-158; Coverage: 99%)
Gene name: folA
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments


Cofactor: Ligand NDP 1 x NDP
2 bound ligands:
Ligand 06U 1 x 06U
Ligand ACT 1 x ACT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: P6122
Unit cell:
a: 78.902Å b: 78.902Å c: 108.118Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.164 0.156 0.233
Expression system: Escherichia coli BL21

Quick links

Citations

3 review citations

Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.
Wróbel et al. (2020)
2 more

2 mentions without citation

Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.
Keshipeddy et al. (2015)
1 more