Regensburg 2013 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 8: Posters: Proteins

BP 8.14: Poster

Montag, 11. März 2013, 17:30–19:30, Poster B2

Reaction mechanism of the enzyme PHM: quantum tunneling and origin of kinetic isotope effects — •Enrique Abad, Judith Rommel, and Johannes Kästner — Computational Biochemistry Group, Institut für Theoretische Chemie, Universität Stuttgart, Stuttgart, Germany

Copper proteins catalyze important biochemical reactions, in particular in the nervous system of higher eukaryotes. PHM is a binuclear Cu protein that stereospecifically hydroxylates one C-H bond of small peptides (such as oxytocin), as a intermediate step for its later amidation.

The reaction mechanism of PHM is still not understood. Several proposals have been made [1, 2], but they have not taken explicitly into account the strong kinetic isotope effects (KIE) present in this reaction [3]. In this work, we perform QM/MM calculations at the DFT level, and tunneling rates for a set of possible reaction paths. We suggest a new reaction mechanism in which tunneling of a H atom is crucial for explaining the KIE.

[1] A. Crespo, et al. (2006) J. Am. Chem. Soc. 128, 12817

[2] P. Chen and E. I. Solomon (2004) J. Am. Chem. Soc. 126, 4991

[3] W. A. Francisco, et al. (2002) J. Am. Chem. Soc. 124, 8194