LAUSR

Shewanella oneidensis, a Gram‐negative γ‐proteobacterium with an extensive redox capacity, possesses four old yellow enzyme (OYE) homologs. Of these, Shewanella yellow enzyme 4 (SYE4) is implicated in resistance to oxidative stress. Here, we present a series of high‐resolution crystal structures for SYE4 in the oxidized and reduced states, and in complex with phenolic ligands and the nitro‐aromatic explosive picric acid. The structures unmask new features, including the identification of a binding platform for long‐chain hydrophobic molecules. Furthermore, we present the first structural observation of a hydride‐Meisenheimer complex of picric acid with a flavoenzyme. Overall, our study exposes the binding promiscuity of SYE4 toward a variety of electrophilic substrates and is consistent with a general detoxification function for SYE4.