Figure 2.

Time is of the essence. Deconvoluting precise impacts of target-specific redox responses remains a challenge because on-target binding and responses are often overwhelmed by off-target mass action of these covalent modifications by highly diffusible and reactive (often bifunctional; see Figure 1, inset) small electrophilic signaling mediators that can react with many targets nonspecifically. The red dot designates a RES signal such as HNE. Inset: dual-reactivity manifested in LDEs such as HNE, potentially resulting in protein cross-links through Schiff base formation (dotted arrow) in addition to conjugate addition (block arrow). Note: Conjugate addition can also occur, but to a lesser extent, with a histdine or lysine (Lys, shown) residue, in addition to with the more nucleophilic residue cysteine (Cys) as shown.