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Literature summary extracted from

  • Galkin, A.; Kulakova, L.; Lim, K.; Chen, C.Z.; Zheng, W.; Turko, I.V.; Herzberg, O.
    Structural basis for inactivation of Giardia lamblia carbamate kinase by disulfiram (2014), J. Biol. Chem., 289, 10502-10509.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.7.2.2 drug development the enzyme is a good drug target and disulfiram may be repurposed as antigiardiasis drug Giardia intestinalis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.2.2 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
2.7.2.2 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

EC Number Metals/Ions Comment Organism Structure
2.7.2.2 Mg2+ required Giardia intestinalis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.2.2 ATP + NH3 + CO2 Giardia intestinalis
-
 ADP + carbamoyl phosphate
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.7.2.2 Giardia intestinalis O97438 assemblage A isolate WB, assemblage B isolate GS/H7, and assemblage A metronidazole-resistant isolate 713M3, gene cbk
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.2.2 trophozoite
-
 Giardia intestinalis
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.2.2 ATP + NH3 + CO2
-
 Giardia intestinalis ADP + carbamoyl phosphate
-
 r

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.2.2 ADP
-
 Giardia intestinalis
2.7.2.2 ATP
-
 Giardia intestinalis

General Information

EC Number General Information Comment Organism
2.7.2.2 metabolism the enzyme catalyzes the final step in the arginine dihydrolase pathway converting ADP and carbamoyl phosphate to ATP and carbamate Giardia intestinalis
2.7.2.2 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
2.7.2.2 physiological function carbamate kinase is an essential Giardia lamblia enzyme Giardia intestinalis