X-ray structure and characterization of carbamate kinase from the human parasite Giardia lamblia

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Apr 1;66(Pt 4):386-90. doi: 10.1107/S1744309110004665. Epub 2010 Mar 26.


Carbamate kinase catalyzes the reversible conversion of carbamoyl phosphate and ADP to ATP and ammonium carbamate, which is hydrolyzed to ammonia and carbonate. The three-dimensional structure of carbamate kinase from the human parasite Giardia lamblia (glCK) has been determined at 3 A resolution. The crystals belonged to the monoclinic space group P2(1), with unit-cell parameters a = 69.77, b = 85.41, c = 102.1 A, beta = 106.8 degrees . The structure was refined to a final R factor of 0.227. The essentiality of glCK together with its absence in humans makes the enzyme an attractive candidate for anti-Giardia drug development. Steady-state kinetic rate constants have been determined. The k(cat) for ATP formation is 319 +/- 9 s(-1). The K(m) values for carbamoyl phosphate and ADP are 85 +/- 6 and 70 +/- 5 microM, respectively. The structure suggests that three invariant lysine residues (Lys131, Lys216 and Lys278) may be involved in the binding of substrates and phosphoryl transfer. The structure of glCK reveals that a glycerol molecule binds in the likely carbamoyl phosphate-binding site.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carbamyl Phosphate / chemistry
  • Carbamyl Phosphate / metabolism
  • Catalytic Domain
  • Crystallography, X-Ray
  • Giardia lamblia / enzymology*
  • Glycerol / chemistry
  • Glycerol / metabolism
  • Models, Molecular
  • Phosphotransferases (Carboxyl Group Acceptor) / chemistry*
  • Phosphotransferases (Carboxyl Group Acceptor) / isolation & purification
  • Phosphotransferases (Carboxyl Group Acceptor) / metabolism
  • Protein Structure, Quaternary
  • Structural Homology, Protein


  • Carbamyl Phosphate
  • Phosphotransferases (Carboxyl Group Acceptor)
  • carbamate kinase
  • Glycerol