With a single fluoride ion, scientists have made it possible to visualize the structure of a noncovalent enzyme-inhibitor complex that couldn’t be seen before (J. Am. Chem. Soc., DOI: 10.1021/ja110877y). Inhibitors and many substrates often bind enzyme active sites covalently after first binding noncovalently at areas just outside those sites. But covalent bonding is such a strong interaction compared with noncovalent binding that the initial noncovalent states cannot be observed when enzyme-inhibitor complexes are crystallized for structural analysis. Raymond C. Stevens, Dale L. Boger, and coworkers at Scripps Research Institute found a way around this dilemma. They were able to crystallize and structurally analyze a noncovalent complex—an α-ketooxadiazole inhibitor bound to fatty acid amide hydrolase—by plugging the enzyme active site’s “oxyanion hole” with fluoride so the inhibitor couldn’t bind covalently. The enzyme adopts an “in action” state in which its active site is poised to catalyze a reaction, suggesting many other applications of the approach, including examining other enzyme structures with active-site residues in action or enzyme complexes with unreacted substrate.