› 5isq

X-ray diffraction
1.9Å resolution

Staphylococcus aureus H30N, F98Y Dihydrofolate Reductase mutant complexed with beta-NADPH and 3'-(3-(2,4-diamino-6-ethylpyrimidin-5-yl)prop-2-yn-1-yl)-4'-methoxy-[1,1'-biphenyl]-4-carboxylic acid (UCP1106)

Released:
DOI: 10.2210/pdb5isq/pdb
PDB entry 5isq coloured by chain, front view.
PDB entry 5isq coloured by chain, side view.
PDB entry 5isq coloured by chain, top view.
Source organism: Staphylococcus aureus
Primary publication:
Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations.
Reeve SM, Scocchera E, Ferreira JJ, G-Dayanandan N, Keshipeddy S, Wright DL, Anderson AC
J Med Chem 59 6493-500 (2016)
PMID: 27308944

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: 160 amino acids
Theoretical weight: 18.39 KDa
Source organism: Staphylococcus aureus
Expression system: Escherichia coli BL21(DE3)
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 NAP 1 x NAP
2 bound ligands:
Ligand U06 1 x U06
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL7-1
Spacegroup: P6122
Unit cell:
a: 78.985Å b: 78.985Å c: 108.686Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.18 0.178 0.222
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

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