Higher order structure (top) and amino acid sequence (bottom) of IFN with elements of secondary structure labeled according to a commonly accepted nomenclature (44). Colored residues are common targets of non-enzymatic or designer PTMs: orange, Cys-17 (alkylation, oxidation, formation of external disulfides, internal disulfide scrambling, replacement with Ser in interferon β1b, PEGylation via thiol-reactive group); yellow, Cys-31 and Cys-141 (disulfide scrambling); cyan, Lys-19 (glycation (86)); magenta, methionine residues (oxidation); and green, Asn-90 (variable glycosylation and deglycosylation).