A qualitative quantum rate model for hydrogen transfer in soybean lipoxygenase

Abstract

The hydrogen transfer reaction catalysed by soybean lipoxygenase (SLO) has been the focus of intense study following observations of a high kinetic isotope effect (KIE). Today high KIEs are generally thought to indicate departure from classical rate theory and are seen as a strong signature of tunnelling of the transferring particle, hydrogen or one of its isotopes, through the reaction energy barrier. In this paper we build a qualitative quantum rate model with few free parameters that describes the dynamics of the transferring particle when it is exposed to energetic potentials exerted by the donor and the acceptor. The enzyme's impact on the dynamics is modelled by an additional energetic term, an oscillatory contribution known as "gating". By varying two key parameters, the gating frequency and the mean donoracceptor separation, the model is able to reproduce well the KIE data for SLO wild-type and a variety of SLO mutants over the experimentally accessible temperature range. While SLO-specific constants have been considered here, it is possible to adapt these for other enzymes.

Proton tunnelling in hydrogen bonds and its implications in an induced-fit model of enzyme catalysis

“…The pseudo-spin term of this state can be thought as the ground state of the interaction Hamiltonian H I = H (13) HB + H (24) HB with large pseudo-spin separations and vanishing hopping constants. When R 13 and R 24 become sufficiently small, a small amount of entanglement is generated through the weak X 1 −H• • • X 3 and X 2 • • • H−X 4 bonds:…”

“…According to the kinetic isotope effects studies, observed rates of several enzyme-catalysed oxidoreduction reactions cannot be explained solely in terms of a semi-classical transition-state theory without a quantum-mechanical correction for the tunnelling of H species [8][9][10][11][12][13][14][15]. Moreover, a number of different studies, including the kinetic isotope experiments [11,12], molecular dynamic simulations [16][17][18], quantum mechanical molecular mechanics calculations [19][20][21][22][23] and qualitative quantum rate models [24] give prominence to the role of the conformational change in promoting tunnelling.…”

Parameter Reliability and Understanding Enzyme Function

“…Whereas the kinetics of enzyme-substrate interactions has often assumed simple diffusion limited, or controlled, collision theory [ 71 ], the maximum value of would be around – M s if every collision between the enzyme and substrate molecule results in the formation of a viable ES complex. Not surprisingly, few enzymes approach this theoretical maximum value [ 72 ], but a few do so, and some even appear to exceed it (e.g., [ 73 ]). As might be expected, cellular crowding affects diffusion rates, as well as protein aggregation and phase separation [ 74 ].…”

Cavity-Altered Thermal Isomerization Rates and Dynamical Resonant Localization in Vibro-Polaritonic Chemistry

“…Unlike quantum mechanical (CRP) rates, k TST (T, η) does not account for tunneling along the reaction path. 41 To include tunneling approximately, a Wigner tunneling correction 34 κ W (T, η) = 1 + 1 24…”

“…( 9), while keeping the remaining parameters of the potential, A 2 and A 4 , constant. To account for barrier fluctuations, we use a simple stochastic averaging procedure originally suggested to model environmentinduced potential fluctuations for a hydrogen transfer reaction in a protein environment 41 .…”