TYMS Human

Thymidylate synthetase, also known as thymidylate synthase (TS), is a crucial enzyme in the de novo synthesis of thymidylate (dTMP), an essential precursor for DNA replication and repair. This enzyme catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) using 5,10-methylenetetrahydrofolate as a cofactor . Thymidylate synthetase is highly conserved across various species, including humans, and plays a pivotal role in maintaining the balance of deoxynucleotide pools within the cell .

Thymidylate synthetase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains an active site where the catalytic reaction occurs. The enzyme’s structure is highly conserved, with bacterial and mammalian TSases sharing remarkable similarities . The active site of thymidylate synthetase binds to both dUMP and the folate cofactor, facilitating the transfer of a methyl group to form dTMP .

The activity of thymidylate synthetase is critical for DNA synthesis and cell proliferation. Inhibition or dysregulation of this enzyme can lead to an imbalance in deoxynucleotide pools, resulting in DNA damage and cell death . Due to its essential role in DNA synthesis, thymidylate synthetase is a target for chemotherapeutic agents, particularly in the treatment of cancer . Overexpression of thymidylate synthetase has been associated with resistance to certain chemotherapeutic drugs, such as 5-fluorouracil (5-FU), making it a significant focus of cancer research .

Human recombinant thymidylate synthetase is produced using recombinant DNA technology, which involves inserting the human TS gene into a suitable expression system, such as Escherichia coli or yeast. This allows for the large-scale production of the enzyme for research and therapeutic purposes. Recombinant thymidylate synthetase retains the same structural and functional properties as the native enzyme, making it a valuable tool for studying enzyme kinetics, drug interactions, and the development of new therapeutic agents .

Thymidylate synthetase is a key target in cancer therapy due to its role in DNA synthesis. Inhibitors of this enzyme, such as 5-FU and its derivatives, are commonly used in the treatment of various cancers, including colorectal, breast, and gastric cancers . Research on thymidylate synthetase also focuses on understanding the mechanisms of drug resistance and developing new strategies to overcome it. Additionally, the enzyme is used in biochemical studies to elucidate the molecular mechanisms of DNA synthesis and repair .