Crystallization (Comment) | Organism |
---|---|
wild-type enzyme or mutant F98Y in ternary complex with cofactor NADPH and inhibitors AR-101, AR-102, or iclaprim, hanging-drop vapour-diffusion technique at 24°C, mixing of 30 mg/ml protein with 5 mM NADPH and 0.3 mg/ml inhibitor in 25% PEG 3350, 200 mM NaCl, and 100 mM bis-tris, pH 5.5, X-ray diffraction structure determination and analysis at 2.1-2.5 A resolution | Staphylococcus aureus |
Protein Variants | Comment | Organism |
---|---|---|
F98Y | site-directed mutagenesis, the mutant enzyme shows reduced sensitivity to inhibitors compared to the wild-type enzyme, structure comparison to the wild-type, overview | Staphylococcus aureus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
AR-101 | i.e. 5-[(2R)-2-cyclopropyl-7,8-dimethoxy-2H-chromene-5-ylmethyl]pyrimidine-2,4-diamine, binding structure from crystal structure, the cyclopropyl-dimethoxychromene moiety interacts with the conserved residues Leu28, Val31, Ile50 and Leu54 forming a hydrophobic pocket in the enzyme | Staphylococcus aureus | |
Ar-102 | i.e. 5-[(2S)-2-cyclopropyl-7,8-dimethoxy-2H-chromene-5-ylmethyl]pyrimidine-2,4-diamine, binding structure from crystal structure, the cyclopropyl-dimethoxychromene moiety interacts with the conserved residues Leu28, Val31, Ile50 and Leu54 forming a hydrophobic pocket in the enzyme | Staphylococcus aureus | |
iclaprim | binding structure from crystal structure | Staphylococcus aureus | |
trimethoprim | - |
Staphylococcus aureus |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Staphylococcus aureus | P0A017 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | the conserved residues Leu28, Val31, Ile50 and Leu54 forming a hydrophobic pocket in the enzyme are the binding site for the p-aminobenzamide moiety of the substrate dihydrofolate | Staphylococcus aureus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
DHFR | - |
Staphylococcus aureus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | - |
Staphylococcus aureus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0000002 | - |
iclaprim | wild-type enzyme | Staphylococcus aureus | |
0.00000022 | - |
Ar-102 | wild-type enzyme | Staphylococcus aureus | |
0.00000023 | - |
AR-101 | wild-type enzyme | Staphylococcus aureus | |
0.0000009 | - |
AR-101 | mutant F98Y | Staphylococcus aureus | |
0.0000026 | - |
iclaprim | mutant F98Y | Staphylococcus aureus | |
0.0000035 | - |
Ar-102 | mutant F98Y | Staphylococcus aureus | |
0.000006 | - |
trimethoprim | wild-type enzyme | Staphylococcus aureus | |
0.0001 | - |
trimethoprim | mutant F98Y | Staphylococcus aureus |