Reaction Mechanism of the Bicopper Enzyme Peptidylglycine α-Hydroxylating Monooxygenase

• DOI: 10.1074/jbc.m114.558494
• Publication Date: 2014-03-26T04:37:02Z
• Authors: Enrique Abad; Judith B. Rommel; Johannes Kästner
• Keywords: Hydrogen atom abstraction; Hydrogen atom; Biocatalysis; Kinetic isotope effect

Peptidylglycine α-hydroxylating monooxygenase is a noninteracting bicopper enzyme that stereospecifically hydroxylates the terminal glycine of small peptides for its later amidation. Neuroendocrine messengers, such as oxytocin, rely on biological activity this enzyme. Each catalytic turnover requires one oxygen molecule, two protons from solvent, and electrons. Despite having been widely studied, consensus reaction mechanism has not yet found. Experiments theoretical studies favor pro-S abstraction hydrogen atom followed by rebinding an OH group. However, several hydrogen-abstracting species have postulated; because are consumed during reaction, protonation states available. An electron transfer between copper atoms could play crucial role catalysis well. This leads to six possible abstracting species. In study, we compare them equal footing. We perform quantum mechanics/molecular mechanics calculations, considering abstraction. Our results suggest most likely before another well reduction rebinding.