UCK2

Uridine-cytidine kinase 2 (UCK2) is an enzyme that in humans is encoded by the UCK2 gene.

The protein encoded by this gene catalyzes the phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively. This is the first step in the production of the pyrimidine nucleoside triphosphates required for RNA and DNA synthesis. In addition, an allele of this gene may play a role in mediating nonhumoral immunity to Hemophilus influenzae type B.

Structure and mechanism

Uridine-cytidine kinase 2 is a tetramer with molecular mass of about 112 kDa. In the UCK2 monomer, the active site is composed of a five-stranded β-sheet, surrounded by five α-helices and a β-hairpin loop. The β-hairpin loop in particular forms a significant portion of a deep binding pocket for the uridine/cytidine substrate to moderate binding and release of substrate and products. Binding specificity for nucleosides is determined by the His-117 and Tyr-112 residues, which hydrogen bond with the 4-amino group or the 6-oxo group of cytidine and uridine, respectively. A magnesium ion is coordinated in the active site by Glu-135, Ser-34, and Asp-62. The Asp-62 residue is responsible for the catalytic activity in the enzyme active site; the acidic side chain of the Asp-62 residue deprotonates the 5'-hydroxyl group on the substrate and activates it to attack the γ-phosphorus of ATP. Structural analyses have shown that the side chain of the catalytic Asp-62 changes conformation before and after the reaction. It has been suggested that this conformational change occurs following phosphorylation, with the negatively charged Asp-62 moving away from the newly attached 5'-phosphate of the UMP/CMP product.