Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling

We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp128b in a reaction dominated by tunneling over È0.6 angstroms. The role of long-range coupled motions in promoting tunneling is controversial. We show that, in this enzyme system, tunneling is promoted by a short-range motion modulating proton-acceptor distance and no long-range coupled motion is required. T he physical basis of the catalytic power of enzymes remains contentious despite sustained and intensive research efforts (1–3). The question of whether enzymes have evolved to use quantum tunneling to the best advantage has provoked a heated debate (4–10)