DCK Human

Deoxycytidine Kinase (dCK) is a crucial enzyme in the nucleoside salvage pathway, responsible for phosphorylating deoxyribonucleosides and their analogues. This enzyme is encoded by the DCK gene in humans and plays a significant role in DNA synthesis and repair. The recombinant form of this enzyme, known as Human Recombinant Deoxycytidine Kinase, is widely used in research and therapeutic applications.

Deoxycytidine Kinase is a homodimer, with each monomer subunit consisting of multiple alpha helices surrounding a beta sheet core . The enzyme has several different protein conformations, which depend on the nucleoside or nucleotide it binds to. dCK can bind to ADP, ATP, UDP, or UTP, and the binding of these phosphoryl donors changes the enzyme’s conformation . This change in conformation determines which nucleoside can bind in the nucleoside binding site .

The primary function of dCK is to phosphorylate deoxycytidine (dC) and convert it into deoxycytidine monophosphate (dCMP) . Additionally, dCK can phosphorylate other preformed nucleosides, such as deoxyadenosine (dA) and deoxyguanosine (dG), converting them into their monophosphate forms . This enzyme is usually the rate-limiting step in the process of converting nucleosides to their deoxynucleoside triphosphate form in the nucleoside salvage pathway .

Human Recombinant Deoxycytidine Kinase is typically produced using recombinant DNA technology. The DCK gene is cloned into an expression vector, which is then introduced into a suitable host cell, such as Escherichia coli or yeast. The host cells are cultured under conditions that promote the expression of the recombinant enzyme. After sufficient growth, the cells are harvested, and the enzyme is purified using various chromatographic techniques.

Deoxycytidine Kinase catalyzes the phosphorylation of deoxyribonucleosides using phosphate groups from ATP and UTP . The enzyme adds the first phosphoryl group to preformed nucleosides, which is a critical step in the nucleoside salvage pathway . This pathway is essential for maintaining the balance of deoxynucleoside triphosphates required for DNA synthesis and repair .

The activity of dCK is regulated by various factors, including the availability of nucleosides and nucleotides, as well as the presence of specific inhibitors and activators . For example, the enzyme’s activity can be enhanced by preincubation with nucleoside derivatives and nonnucleoside genotoxic agents . Conversely, protein phosphatase inhibitors can decrease dCK activity, suggesting a regulatory role for reversible protein phosphorylation in the activation process .

Deoxycytidine Kinase has garnered significant interest in biomedical research due to its potential as a therapeutic target for various types of cancer . The enzyme’s ability to phosphorylate nucleoside analogues makes it a critical player in the activation of several anticancer and antiviral drugs . For instance, dCK is involved in the activation of drugs such as lamivudine (3TC), cytarabine (ara-C), cladribine (CdA), and gemcitabine (dFdC), which are used in the treatment of cancer and viral infections .