CRYSTALLOGRAPHIC OBSERVATION OF A TRAPPED TETRAHEDRAL INTERMEDIATE INA METALLOENZYME

Formation of tetrahedral transition intermediates is a key step in man y enzyme catalyzed reactions, Much of our understanding of these and o ther intermediates, at the atomic level, has come from crystallographi c studies of very few enzymes with bound, synthetic, transition-state analogues. Here we present the structure of adenosine deaminase, a zin c-metalloenzyme critical in both purine metabolism and development of the lymphoid system, having performed a stereospecific hydroxide addit ion to the C6 of inosine, This addition causes the O6 oxygen of inosin e to assume an orientation analogous to the position of the amino leav ing group of the tetrahedral intermediate in the enzyme-catalyzed hydr olytic deamination of adenosine to inosine.