Hunting down hydrogen: applying neutron macromolecular crystallography to galectins

Galectins are a medically important family of small, soluble carbohydrate-binding proteins that have been implicated in a wide variety of diseases, and are therefore targets for the development of new drugs. Many X-ray crystal structures of small molecules in complex with galectins have been determined and have given invaluable information on how natural ligands and synthetic inhibitors are recognized. However, until now the hydrogen-bonding patterns involved in ligand recognition have been a matter of informed guesswork, as X-ray crystallography can't reliably tell us where hydrogen atoms are positioned. We describe how neutron macromolecular crystallography has been applied to galectins for the first time to shed light on this question.