Molecular glue everywhere: Metabolites join the party.

Endogenous purine nucleotides and thiopurine drugs act as molecular glues to inhibit purine synthesis by linking PPAT to NUDT5.

• Why it matters: Understanding how small molecules regulate enzyme interactions is crucial for developing targeted therapies and elucidating metabolic control mechanisms.
• What they did: Witus et al. used structural and biochemical approaches to demonstrate that purine metabolites and drugs promote PPAT-NUDT5 tethering through a flexible, cooperative binding pocket.
• The result: This discovery reveals a widespread role for metabolites as molecular glues, opening new avenues for drug design and metabolic regulation strategies.