Thymidylate synthase

Thymidylate synthase (TS) is an enzyme that plays a crucial role in the replication of the cell's DNA. It is part of the folate pathway, which is responsible for the formation of tetrahydrofolate and its derivatives. TS is the target of many chemotherapeutic agents, including 5-fluorouracil and raltitrexed.

Function

Thymidylate synthase catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). This reaction is crucial in the DNA replication process because dTMP is required for the synthesis of DNA. Without sufficient dTMP, cells can undergo "thymineless death."

Structure

The structure of thymidylate synthase is highly conserved among different species, indicating its importance in cellular function. The enzyme is a homodimer, with each monomer consisting of a single polypeptide chain. The active site, where the catalytic reaction occurs, is located at the interface of the two monomers.

Clinical significance

Because of its role in DNA replication, thymidylate synthase is a target for chemotherapeutic drugs. These drugs inhibit the function of TS, preventing the synthesis of new DNA and thus stopping the proliferation of cancer cells. Examples of such drugs include 5-fluorouracil and raltitrexed.

See also

• DNA replication
• Chemotherapy
• 5-fluorouracil
• Raltitrexed

References

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Thymidylate_synthase

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  Thymidylate_synthase
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  Simple Cycle of Thymidylate Synthase
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  Mechanism of Thymidylate Synthase
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  Thymidylate Synthase as a homodimer
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  Active site of Thymidylate Synthase