Exercise: Using the STITCH database

The STITCH database contains functional associations among proteins and small molecules.

Try searching STITCH with the human thymidylate synthase (TYMS) protein as input. The resulting network includes several small molecules.

Questions:

  • Can you identify the products of thymidylate synthase among them?
  • Are the reactants also present in the network?

Sometimes the proteins or small molecules that you search for may not be immediately shown by STITCH. To find what you are looking for you may have to extend the network.

Questions:

  • Do the small molecules that were missing in the questions above appear when clicking the Add nodes button?
  • Can you construct a clearer network with fewer interactions by changing the network parameters at the bottom of the page?

Thymidine is required for DNA replication and repair to take place, and inhibition of thymidine synthase is thus harmful to proliferating cells. Indeed, most of the small molecules in the network are drugs used for chemotherapy.

Questions:

  • Are these drugs structurally similar to each other?
  • Are they similar to substrate of thymidylate synthase?
  • Can you suggest a mechanism of action?

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