Mechanisms of O 2 Activation by Mononuclear Non-Heme Iron Enzymes

• Published in: Biochemistry (Easton) Vol. 60; no. 46; pp. 3497 - 3506
• Main Authors: Solomon, Edward I, DeWeese, Dory E, Babicz, Jr, Jeffrey T
• Format: Journal Article
• Language: English
• Published: United States 23.11.2021
• Subjects: Catalytic Domain; Cysteine Dioxygenase - chemistry; Cysteine Dioxygenase - metabolism; Electron Transport Complex III - chemistry; Electron Transport Complex III - metabolism; Iron - metabolism; Ketoglutaric Acids - chemistry; Ketoglutaric Acids - metabolism; Oxygen - metabolism; Pterins - metabolism; Superoxides - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/acs.biochem.1c00370

Two major subclasses of mononuclear non-heme ferrous enzymes use two electron-donating organic cofactors (α-ketoglutarate or pterin) to activate O to form Fe ═O intermediates that further react with their substrates through hydrogen atom abstraction or electrophilic aromatic substitution. New spectroscopic methodologies have been developed, enabling the study of the active sites in these enzymes and their oxygen intermediates. Coupled to electronic structure calculations, the results of these spectroscopies provide fundamental insight into mechanism. This Perspective summarizes the results of these studies in elucidating the mechanism of dioxygen activation to form the Fe ═O intermediate and the geometric and electronic structure of this intermediate that enables its high reactivity and selectivity in product formation.