Guanylate kinase 1 (GUK1)

Guanylate kinase 1 is an essential cytoplasmic enzyme that catalyzes the phosphorylation of guanosine monophosphate (GMP) to guanosine diphosphate (GDP) using ATP. It is the principal enzyme responsible for maintaining the balance of nucleotide pools required for DNA and RNA synthesis, cell proliferation, and cell survival. Guanylate kinase 1 also plays a critical role in the metabolic activation of several nucleoside analog prodrugs used in the treatment of cancer and viral infections, such as 6-thioguanine, 6-mercaptopurine, ganciclovir, and acyclovir. Functional loss or inhibition of this enzyme disrupts nucleotide homeostasis and can impair cancer cell viability. Structure-function studies show that human guanylate kinase consists of three domains—LID, GMP-binding, and CORE domains. Its pharmacological relevance makes it an emerging target for anticancer and antiviral therapy.

Other names

GMKhGMPK

Prodrug activation: catalyzes phosphorylation of nucleoside analogs for antineoplastic and antiviral effect