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203,241,242 In addition, most of these 12 structural classes also harbor representatives that control the adaptive response to cellular reactive oxygen species (ROS), e.g., superoxide and peroxides, reactive nitrogen species (RNS), e.g., GSNO and NOx, reactive electrophile species (RES), e.g., formaldehyde, quinones and the recently described reactive sulfur species (RSS), e.g., thiol persulfides or more generally supersulfides. 243,244 We review how sequence diversity in each structural family can be represented by clusters of closely related sequences 239,245,246 and interpreted in terms of a conserved metal binding or sensory motif, thereby defining the cognate inducer with greater confidence