Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for antifolate drugs. The parasite develops resistance to several used antifolates via mutations in the active site, e.g. point mutations of residues Ala16, Ile51, Cys59, Ser108 and Ile164, overview | Plasmodium falciparum |
Protein Variants | Comment | Organism |
---|---|---|
A16V | point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine | Plasmodium falciparum |
A16V/N51I/C59R/S108N | point mutations of the active site residues lead to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine, binding structure modelling, overview | Plasmodium falciparum |
C59R | point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine | Plasmodium falciparum |
C59R/S108N | point mutations of the active site residues lead to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine, binding structure modelling, overview | Plasmodium falciparum |
N51I | point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine | Plasmodium falciparum |
S108N | point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine | Plasmodium falciparum |
S108T | point mutation of the active site residue leads to a widespread resistance of the parasite to the drugs cycloguanil and pyrimethamine | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(1E)-1-[4-[(3,5-dichloropyridin-4-yl)oxy]phenyl]ethanone thiosemicarbazone | - |
Plasmodium falciparum | |
1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine | - |
Plasmodium falciparum | |
1-[3-(3,4-dichlorophenoxy)propyloxy]-5-isopropylbiguanide | i.e. PS-16 | Plasmodium falciparum | |
1-[3-(4-chlorophenoxy)propyloxy]-5-isopropylbiguanide | i.e. PS-33 | Plasmodium falciparum | |
2,3-bis(hydrazino)quinoxaline | - |
Plasmodium falciparum | |
2-[[(4-[[(2-amino-4-oxo-3,4-dihydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]phenyl)carbonyl]amino]hexanedioic acid | - |
Plasmodium falciparum | |
2-[[1-(3-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl]carbonyl]-N-prop-2-en-1-ylhydrazinecarbothioamide | - |
Plasmodium falciparum | |
3-[[(4-chlorophenyl)sulfonyl]methyl]-N'-hydroxybenzenecarboximidamide | - |
Plasmodium falciparum | |
4-(benzyloxy)benzaldehyde thiosemicarbazone | - |
Plasmodium falciparum | |
4-chloro-N-[4-(hydroxycarbamimidoyl)benzyl]benzamide | - |
Plasmodium falciparum | |
4-[(3,5-dichloropyridin-4-yl)oxy]-N'-hydroxybenzenecarboximidamide | - |
Plasmodium falciparum | |
4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy]benzaldehyde thiosemicarbazone | - |
Plasmodium falciparum | |
6-[[(2,5-dimethylphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | identified from docking studies | Plasmodium falciparum | |
6-[[(3,4-dimethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | - |
Plasmodium falciparum | |
benzaldehyde semicarbazone | - |
Plasmodium falciparum | |
chlorocycloguanil | - |
Plasmodium falciparum | |
cycloguanil | and prodrug proguanil | Plasmodium falciparum | |
methotrexate | - |
Plasmodium falciparum | |
methyl 5-[(1E)-N-carbamoylethanehydrazonoyl]-2,3'-bithiophene-5'-carboxylate | - |
Plasmodium falciparum | |
pyrimethamine | - |
Plasmodium falciparum | |
trimepthoprim | - |
Plasmodium falciparum | |
WR99210 | and PS-15 W99210 prodrug. Active site binding structure of wild-type enzyme, and mutants C59R/S108N and A16V/N51I/C59R/S108N, overview | Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | Plasmodium falciparum | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium falciparum | - |
- |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ | Ala16, Ile51, Cys59, Ser108 and Ile164 are active site residues, catalytic mechanism, overview | Plasmodium falciparum |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | - |
Plasmodium falciparum | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r |
Synonyms | Comment | Organism |
---|---|---|
DHFR | - |
Plasmodium falciparum |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Plasmodium falciparum | |
NADPH | - |
Plasmodium falciparum |