Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a good drug target and disulfiram may be repurposed as antigiardiasis drug | Giardia intestinalis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
Disulfiram | the anti-alcoholism drug kills the trophozoites and inhibits the enzyme. Disulfiram acts by modifying Cys-242 adjacent to the active site and cures giardiasis in mice. The compound thiocarbamoylates Cys242, a residue located at the edge of the active site. The modified Cys242 prevents a conformational transition of a loop adjacent to the ADP/ATP binding site, which is required for the stacking of Tyr245 side chain against the adenine moiety | Giardia intestinalis | |
metronidazole | irreversible inactivation mechanism, the thiuram compounds can circumvent the resistance mechanism that renders metronidazole ineffectiveness in drug resistance cases of giardiasis | Giardia intestinalis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Giardia intestinalis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + NH3 + CO2 | Giardia intestinalis | - |
ADP + carbamoyl phosphate | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Giardia intestinalis | O97438 | assemblage A isolate WB, assemblage B isolate GS/H7, and assemblage A metronidazole-resistant isolate 713M3, gene cbk | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
trophozoite | - |
Giardia intestinalis | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + NH3 + CO2 | - |
Giardia intestinalis | ADP + carbamoyl phosphate | - |
r |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ADP | - |
Giardia intestinalis | |
ATP | - |
Giardia intestinalis |
General Information | Comment | Organism |
---|---|---|
metabolism | the enzyme catalyzes the final step in the arginine dihydrolase pathway converting ADP and carbamoyl phosphate to ATP and carbamate | Giardia intestinalis |
additional information | mdelling of the environment of Cys242 superposed in three conformational states, the AMP-PNP bound structure, the citric acid bound structure, and the thiocarbamoylated structure, overview. Modification of Cys242 interferes with the conformational transition that accompanies nucleotide binding, whereas the citric acid binding remains unaltered and the auxiliary domain is in the closed conformation | Giardia intestinalis |
physiological function | carbamate kinase is an essential Giardia lamblia enzyme | Giardia intestinalis |