› 4km2

X-ray diffraction
1.4Å resolution

Crystal structure of Dihydrofolate reductase from Mycobacterium tuberculosis in an open conformation in complex with trimethoprim

Released:
DOI: 10.2210/pdb4km2/pdb
PDB entry 4km2 coloured by chain, front view.
PDB entry 4km2 coloured by chain, side view.
PDB entry 4km2 coloured by chain, top view.
Source organism: Mycobacterium tuberculosis
Primary publication:
Mycobacterium tuberculosis dihydrofolate reductase reveals two conformational states and a possible low affinity mechanism to antifolate drugs.
Dias MV, Tyrakis P, Domingues RR, Paes Leme AF, Blundell TL
Structure 22 94-103 (2014)
PMID: 24210757

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-161901 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chains: A, B
Molecule details ›
Chains: A, B
Length: 179 amino acids
Theoretical weight: 19.83 KDa
Source organism: Mycobacterium tuberculosis
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P9WNX1 (Residues: 3-161; Coverage: 99%)
Gene names: MTV002.28c, Rv2763c, dfrA, folA
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments

2 bound ligands:
Ligand ATR 2 x ATR
Ligand TOP 2 x TOP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06DA
Spacegroup: P212121
Unit cell:
a: 64.16Å b: 65.28Å c: 79.75Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.144 0.141 0.201
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

3 review citations

Mycobacterium tuberculosis folate metabolism and the mechanistic basis for para-aminosalicylic acid susceptibility and resistance.
Minato et al. (2015)
2 more

9 mentions without citation

Bioactive Alkaloids from Genus Aspergillus: Mechanistic Interpretation of Their Antimicrobial and Potential SARS-CoV-2 Inhibitory Activity Using Molecular Modelling.
Youssef et al. (2021)
8 more