Pressure effects on enzyme-catalyzed quantum tunneling events arise from protein-specific structural and dynamic changes

Sam Hay, Linus O. Johannissen, Parvinder Hothi, Michael J. Sutcliffe, Nigel S. Scrutton

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The rate and kinetic isotope effect (KIE) on proton transfer during the aromatic amine dehydrogenase-catalyzed reaction with phenylethylamine shows complex pressure and temperature dependences. We are able to rationalize these effects within an environmentally coupled tunneling model based on constant pressure molecular dynamics (MD) simulations. As pressure appears to act anisotropically on the enzyme, perturbation of the reaction coordinate (donor-acceptor compression) is, in this case, marginal. Therefore, while we have previously demonstrated that pressure and temperature dependences can be used to infer H-tunneling and the involvement of promoting vibrations, these effects should not be used in the absence of atomistic insight, as they can vary greatly for different enzymes. We show that a pressure-dependent KIE is not a definitive hallmark of quantum mechanical H-tunneling during an enzyme-catalyzed reaction and that pressure-independent KIEs cannot be used to exclude tunneling contributions or a role for promoting vibrations in the enzyme-catalyzed reaction. We conclude that coupling of MD calculations with experimental rate and KIE studies is required to provide atomistic understanding of pressure effects in enzyme-catalyzed reactions. © 2012 American Chemical Society.
    Original languageEnglish
    Pages (from-to)9749-9754
    Number of pages5
    JournalJournal of the American Chemical Society
    Volume134
    Issue number23
    DOIs
    Publication statusPublished - 13 Jun 2012

    Fingerprint

    Dive into the research topics of 'Pressure effects on enzyme-catalyzed quantum tunneling events arise from protein-specific structural and dynamic changes'. Together they form a unique fingerprint.

    Cite this