Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling

• Published in: Science (American Association for the Advancement of Science) Vol. 312; no. 5771; pp. 237 - 241
• Main Authors: Masgrau, Laura, Roujeinikova, Anna, Johannissen, Linus O, Hothi, Parvinder, Basran, Jaswir, Ranaghan, Kara E, Mulholland, Adrian J, Sutcliffe, Michael J, Scrutton, Nigel S, Leys, David
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 14.04.2006; The American Association for the Advancement of Science
• Subjects: Alcaligenes faecalis - enzymology; Analytical, structural and metabolic biochemistry; Aspartic Acid - chemistry; Atoms; Binding Sites; Biochemistry; Biological and medical sciences; Catalysis; Chemical Phenomena; Chemistry; Chemistry, Physical; Computer Simulation; Crystal structure; Crystallography, X-Ray; Crystals; Enzymes; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods; Hydrogen bonds; Kinetics; Models, Chemical; Molecules; Motion; Oxidation; Oxidation-Reduction; Oxidoreductases Acting on CH-NH Group Donors - chemistry; Oxidoreductases Acting on CH-NH Group Donors - metabolism; Oxygen - chemistry; Protons; Quantum tunneling; Temperature; Thermodynamics; Tryptamines - metabolism; Water - chemistry; Reaction intermediate; Proton; Tunnel effect; Enzymatic reaction; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1126002

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 Asp¹²⁸{szligbeta} in a reaction dominated by tunneling over [approximately]0.6 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.