hydroxyproline dehydratases , arylacetate decarboxylases , choline and isethionate lyases . Their common reactive feature is either the formation, cleavage, or rearrangement of C-C, C-O, C-N, or C-S bonds in biomolecules via radical-based addition or elimination mechanisms . Most GREs contain a homologous large subunit of approximately 100 kDa, which forms a conserved fold, consisting of a 10-stranded -barrel with strands of alternating orientations, and two finger loops protruding towards the center and facing each other from opposite sides of the inner wall. Each of these loops carries a strictly conserved amino acid at its tip which are crucial for the reactivity of GRE: a glycine residue located close to the C-terminus and a cysteine at around the middle of the sequences of the primary subunits (see . All GRE are initially synthesized in a catalytically inactive state and need to be converted to the active, radical-containing state by a separate activating enzyme, which is a member of the S-adenosylmethionine (SAM)-dependent radical enzymes. The activating enzymes contain a bound SAM cofactor at a special Fe4S4 cluster in their active centers and form a productive reaction complex with the conserved Gly residues of the corresponding GRE, which are assumed to be pulled out of the folded GRE structures together with their C-terminal ends during activation . The activating enzyme then transfers one electron from a lowpotential donor like ferredoxin or flavodoxin to the bound SAM cofactor, reducing it to methionine and a Fe-bound deoxyadenosine radical, which in turn removes the pro-S hydrogen of the conserved Gly residue while being reduced to 5'-deoxyadenosine .