Iron-sulfur cluster radical generator

Figure 6 A general mechanism for reactions catalyzed by radical SAM enzymes, where SAM is utilized as either a cofactor or a substrate. The protein backbone and iron-sulfur cluster were generated using PyMol and PDB id ScbS.pdb.

There are no direct chemical models for cleaving a sulfiir-carbon bond using iron-sulfur clusters however, several suggestions have been advanced to explain how a S -deoxyadenosyl S -radical might be generated from SAM. One of the earliest proposals implicated an... 

Figure 11. Mechanisms for generating a 5 -deoxyadenosyl 5 -radical. (A) Model invoking an iron-carbon bond (B) model invoking a n,3-S-carbon bond (C) model invoking electron transfer from the iron-sulfur cluster to SAM.

Spore Photoproduct Lyase. The DNA in spores is in A-form because of dehydration. As a consequence, when spores are exposed to UV, the stereochemistry of the bases is not conducive to the formation of cyclobutane pyrimidine dimers or (6-4) photoproducts. Instead, UV induces the formation of 5-thyminyl-5,6-dihydrothymine or spore photoproduct (SP). This lesion is repaired by a 40-kDa enzyme called SP lyase. The enzyme is an iron-sulfur [4Fe-4S] protein that employs S-adenosyl-methionine (AdoMet) as a catalytic cofactor and carries out repair by a radical mechanism (6) (Fig. 2). In this mechanism, the reduced [Fe-S] center cleaves AdoMet to generate a 5 -deoxyadenosyl radical intermediate and methionine. The radical then abstracts an H-atom from C-6 of the SP. The resulting substrate radical undergoes bond cleavage to generate a product radical. The latter abstracts an H-atom from the 5 deoxyadenosine to form canonical thymines and a 5 deoxyadenosyl radical. Finally, the catalytic cycle is closed by electron transfer back to the [Fe-S] cluster concomitant with the formation of AdoMet (6). 

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