Avoiding the road less traveled: how the topology of enzyme-substrate complexes can dictate product selection.

Enzymes are remarkable not only in their ability to enhance reaction rates, but also because they do so selectively, directing reactive intermediates toward only one of multiple potential products. 1-Aminocyclopropane-1-carboxylate (ACC) synthase and 7,8-diaminopelargonic acid synthase are pyridoxal 5'-phosphate-dependent enzymes that utilize S-adenosyl-l-methionine as a substrate but yield different products. The former produces ACC by alpha,gamma-elimination, while the latter makes S-adenosyl-4-methylthio-2-oxobutanoate by transamination. The mechanisms of these two reactions are the same up to the formation of a quinonoid intermediate, from which they diverge. This Account explores how the active-site topology of the enzyme-intermediate complexes decides this pathway bifurcation.