Formation of tetrahedral transition intermediates is a key step in many enzyme catalyzed reactions. Much of our understanding of these and other intermediates, at the atomic level, has come from crystallographic studies of very few enzymes with bound, synthetic, transition-state analogues. Here we present the structure of adenosine deaminase, a zinc-metalloenzyme critical in both purine metabolism and development of the lymphoid system, having performed a stereospecific hydroxide addition to the C6 of inosine. This addition causes the O6 oxygen of inosine to assume an orientation analogous to the position of the amino leaving group of the tetrahedral intermediate in the enzyme-catalyzed hydrolytic deamination of adenosine to inosine.