title: Proton tunneling in aromatic amine dehydrogenase is driven by a short-range sub-picosecond promoting vibration: consistency of simulation and theory with experiment.
abstract: Hydrogen transfer, an essential component of most biological reactions, is a quantum problem. However, the proposed role of compressive motion in promoting enzymatic H-transfer is contentious. Using molecular dynamics simulations and density functional theory (DFT) calculations, we show that, during proton tunneling in the oxidative deamination of tryptamine catalyzed by the enzyme aromatic amine dehydrogenase (AADH), a sub-picosecond promoting vibration is inherent to the iminoquinone intermediate. We show by numerical modeling that this short-range vibration, with a frequency of approximately 165 cm-1, is consistent with "gating" motion in the hydrogen tunneling model of Kuznetsov and Ulstrup (Kuznetsov, A. M.; Ulstrup, J. Can. J. Chem. 1999, 77, 1085) in an enzymatic reaction with an observed protium/deuterium kinetic isotope effect that is not measurably temperature-dependent.
authors.affiliation: Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science, and Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
authors.forename: Linus O
authors.initials: LO
authors.lastname: Johannissen
authors.forename: Sam
authors.initials: S
authors.lastname: Hay
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Scrutton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sutcliffe
mesh_terms: D003198:Computer Simulation; D006859:Hydrogen / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry*; D011522:Protons; D011809:Quinones / Q000737:chemistry; D014363:Tryptamines / Q000737:chemistry; D014732:Vibration
chemical_list: D011522:Protons; D011809:Quinones; D014363:Tryptamines; C116897:iminoquinone; C030820:tryptamine; D006859:Hydrogen; D000587:Oxidoreductases Acting on CH-NH Group Donors; C037193:aromatic amine dehydrogenase