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Thymidylate synthase

Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage. Thymidylate synthase (TS) plays a crucial role in the early stages of DNA biosynthesis. DNA damage or deletion occur on a daily basis as a result of both endogenous and environmental factors. Such environmental factors include ultraviolet damage and cigarette smoke that contain a variety of carcinogens. Therefore, synthesis and insertion of healthy DNA is vital for normal body functions and avoidance of cancerous activity. In addition, inhibition in synthesis of important nucleotides necessary for cell growth is important. For this reason, TS has become an important target for cancer treatment by means of chemotherapy. The sensitivity of TS to succumb to TS inhibitors is a key part to its success as treatment for colorectal, pancreatic, ovarian, gastric, and breast cancers. Here you can see a crystal structure of the enzyme from Thermotoga maritima determined in complex with a flavin cofactor (PDB code: 7NDZ)

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Thymidylate synthase
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Thymidylate synthase

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