Elucidating enzyme mechanism and intrinsic chemical properties of short-lived intermediates in the catalytic cycles of cysteine dioxygenase and taurine/alpha-ketoglutarate dioxygenase

作者：de Visser Sam P^*

来源：Coordination Chemistry Reviews, 2009, 253(5-6): 754-768.

DOI：10.1016/j.ccr.2008.05.001

• Density functional theory
• Enzyme catalysis
• Enzyme models
• Oxygen activation
• Non-heme systems

In this review paper theoretical insights obtained through Studies of non-heme iron-containing enzymes are discussed. In particular, research on oxygen-utilizing enzymes with a 2-His/1-Asp or 3-His structural motif is the focus of this work with recent examples from studies of cysteine dioxygenase (CDO) and taurine/alpha-ketoglutarate dioxygenase (TauD) enzymes. Thus, theoretical modeling can be extremely useful in the characterization of short-lived intermediates which either cannot be detected experimentally or have a lifetime that is too short to enable spectroscopic characterization. This paper gives an overview of the knowledge of the catalytic cycles of CDO and TauD with particular emphasis on the processes obtained after dioxygen binding. CDO uses molecular oxygen and transfers both oxygen atoms to cysteine to form cysteine sulfinic acid products. By contrast, in TauD the first oxygen atom of O(2) is donated to alpha-ketoglutarate to give succinate, carbon dioxide and an oxo-iron active species. The latter is the oxidant that is able to abstract a hydrogen atom from a substrate and rebounds the hydroxyl group to form hydroxylated products. The theoretical (density functional theory (DFT)) studies show that the first step in this dioxygen activation process is the rate-determining step and that the reactions leading to products are highly exothermic as Would be expected from an efficient catalytic cycle of an enzyme. Furthermore, theory predicts TauD to be a much More aggressive and efficient catalyst then for instance monoxygenase enzymes such as the cytochromes P450 (P450s). Non-heme enzymes generally react with substrates via single-state reactivity (SSR) patterns on a dominant quintet spin-state surface. Theory has found no evidence of possible alternative oxidants in the reaction mechanisms. The theoretical studies give fundamental insight into processes that proceed too fast to be experimentally studied and give answers to questions regarding the efficiency and nature of the oxidizing species of this fascinating class of enzymes.

• 出版日期2009-3