By using X-ray crystallography, researchers have learned how a sugar-transferring enzyme recognizes peptide sequences that trigger a common protein modification reaction—asparagine-linked glycosylation (Nature, DOI: 10.1038/nature10151). Saccharide attachment at asparagine’s side-chain nitrogen is important for protein folding, cell-cell communication, and more, but researchers know little about the attachment process. It requires either a serine or threonine to be two residues away from the asparagine to be modified, but it’s not clear how asparagine’s nitrogen, a poor nucleophile, gets activated for modification. To answer that question, Kaspar P. Locher, Christian Lizak, and coworkers at ETH Zurich crystallized a bacterial transferase together with a peptide substrate. They found that the hydroxyl-containing amino acid helps the enzyme recognize the substrate, but it doesn’t facilitate the reaction. That job belongs to an aspartate and a glutamate in the transferase, which juice up the asparagine by forming hydrogen bonds to its amide protons. The team says more structures need to be solved to fully understand the reaction.