9s4c
diFe-Sulerythin_E126A reduced
Structural highlights
FunctionPublication Abstract from PubMedA variety of non-heme diiron enzymes employ a conserved 2-His-4-carboxylate motif to coordinate a dinuclear Fe site and activate dioxygen for diverse types of reactions. Two of the carboxylate residues act as bridging ligands between the Fe ions. As the type and coordination geometry of the bridging ligands in the diferrous state are thought to modulate reactivity, they were used to group diiron oxygenases into three structural subclasses. Here, we use the small diiron-enzyme sulerythrin as a model to demonstrate that replacements of the bridging carboxylate amino acids allow us to decrease the distance between the two Fe ions, change the coordination of the bridging ligands from 1,3-carboxylates to 1,1-carboxylates and generate all three structural subclasses of diferrous active sites within the same protein scaffold. In addition to the known classes, we generated a coordination mode containing two 1,1-carboxylate bridges. The resulting changes in the Fe coordination also alter the nature of the diferric (hydro)peroxo intermediates formed upon reaction with O(2). Finally, we show that modulating the carboxylate bridges influences the reactivity of sulerythrin with O(2). We establish sulerythrin as a versatile platform to engineer distinct diFe centers by a few exchanges, producing various stable (hydro)peroxo intermediates for further studies. O(2) Activation at an Enzymatic Diiron Site: Bridging Ligand Substitutions Alter Diferric-(Hydro)peroxo States.,Jeoung JH, Runger S, Weisser K, Ruickoldt J, Bhattacharya S, Limberg C, Dobbek H Angew Chem Int Ed Engl. 2026 Jan 28;65(5):e19180. doi: 10.1002/anie.202519180. , Epub 2025 Dec 26. PMID:41452222[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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