A crystallographic view of the reaction cycle in iron(II) and 2‐(oxo)‐glutarate‐dependent oxygenases

Iron(II)‐ and 2‐(oxo)‐glutarate‐ (Fe/2OG) dependent oxygenases are a large and functionally diverse family of oxidative tailoring enzymes, the majority of which are hydroxylases. Many other outcomes are possible, including halogenation, stereoinversion, cyclization, and desaturation reactions, but the structural adaptations that enable alternative transformations are not fully understood. All Fe/2OG enzymes, regardless of outcome, proceed through an Fe(IV)‐oxo intermediate that has been isolated in solution but has not been characterized crystallographically. We have determined high‐resolution x‐ray crystal structures of four distinct states in the reaction pathway of an Fe/2OG hydroxylase, including a previously unobserved intermediate. The study reveals key second‐sphere structural changes during the reaction cycle that explain known reactivity patterns in Fe/2OG enzymes and provide new opportunities for functional prediction and protein engineering in the super family. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .