The role of reaction energy and hydrogen bonding in the reaction path of enzymatic proton transfers

Abstract

The reaction path of the Interacting‐State Model is used with the Transition‐State Theory and the semiclassical correction for tunneling (ISM/scTST) to calculate proton transfer rates in rate‐determining CH bond breaking by enzymes such as mandelate racemase, triose‐phosphate isomerase, methylamine dehydrogenase (MADH), and aromatic amine dehydrogenase (AADH), as well as of the analogous uncatalyzed proton transfers in aqueous solution. This method employs the reaction energy, the bond distances in reactants and products, and properties of the reactive bonds to calculate the proton transfer rates. The comparison between the molecular factors that control reactivity in solution and in the enzymes reveals the following salient features of enzyme catalysis: (1) the change from a bimolecular reaction in solution to an intramolecular reaction with negligible activation entropy in the enzyme; (2) energetic stabilization of the intermediates; and (3) extreme tunneling corrections when hydrogen bonding to a carbon atom is present in the reaction path. Copyright © 2008 John Wiley & Sons, Ltd.

Barrier Compression and Its Contribution to Both Classical and Quantum Mechanical Aspects of Enzyme Catalysis

“…Calculation of the partition functions is nontrivial, as these require knowledge of all the vibrations in the system. However, for a preorganized enzyme active site, there is expected to be little activation entropy and Q z (T) z Q r (T) (see (40) and references therein). We will set the ratio of partition factors to unity in this study-equivalent to assuming that 3 0 z DG z .…”

Computer simulations of quantum tunnelling in enzyme-catalysed hydrogen transfer reactions

“…However, correction by the same method makes the two oxygens of Asp428β in the MADH/methylamine system equivalent in terms of reaction barrier and OD1 is then favoured in terms of reaction energy. Barroso et al (2009) have studied the effect of reaction energy and hydrogen bonds on proton transfers in several enzymes including AADH and MADH using an ISM/scTST approach (see section 4.1) This parameterized model predicts that proton abstraction by OD1 is more favourable than by OD2 of the catalytic aspartate base in both the AADH/tryptamine and MADH/methylamine reactions.…”

Photoacid for Extremely Long-Lived and Reversible pH-Jumps

“…ISM has been described in detail in various recent publications, 16,17,19 including applications to proton transfer reactions in solution 16,20 and in enzymes. 18,21 Briefly, the classical reaction path of ISM for the general proton transfer reaction is a linear interpolation between the Morse curves of HA and HB along the reaction coordinate where n is the HB bond order and the classical reaction energy is pK AH and pK BH are the thermodynamic acidity constants of AH and BH, p A (p B ) is the number of equivalent protons in AH (BH), q A (q B ) is the number of equivalent basic sites in AH (BH), and Z AH (Z BH ) is the zero-point energy of the AH (BH) bond. The presence of hydrogen-bonded intermediates is included in this reaction path using the Lippincott-Schroeder potential.…”