Metallo-enzymatic systems can be further complicated by the use of multiple metal clusters within the same protein. This is particularly true of a subset of the large Radical- SAM enzyme family, which contains two [4Fe-4S] clusters. Several enzyme systems involved in complex transfer RNA modification, protein modification, cofactor biosynthesis, antibiotic biosynthesis and all kinds of metabolic reactions are presented. It is now well established that this complexity is linked to the need to activate two stable substrates, notably in highly reactive intermediate radical species, and to make them react together in a concerted fashion. Indeed, the first cluster is most commonly used to bind SAM (S-adenosylmethionine) and activate it into a 5'-deoxyadenosyl radical. This can then react with the second substrate, which is attached to and activated by the second cluster. The situation is even more complex when such systems work on three substrates, as is the case in certain transfer RNA or protein modification reactions. In this case, the active site enables the macromolecule to be positioned close to the two clusters, as demonstrated crystallographically in the case of the RimO protein.
10:00 - 11:00
Lecture
Radical biotransformations : multiple iron-sulfur clusters
Marc Fontecave
10:00 - 11:00