Distinguished Lecture Series Guest Speaker:
Novartis Professor of Chemistry, Massachusetts Institute of Technology
Professor of Biology, Massachusetts Institute of Technology
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides providing the monomeric building blocks required for DNA replication and repair. The E. coli class Ia RNR has a subunit (β2) that contains a diferric-tyrosyl radical (Y•) cofactor, while the E. coli class Ib RNR β2 subunit contains a dimanganese-Y• cofactor. In both cases, the cofactors are essential for catalytic activity. Our recent studies suggest that these cofactors are biosynthesized and maintained using proteins designed for this purpose. In the class Ia β2, YfaE, a ferredoxin-like protein has been identified and in the case of class Ib β2, NrdI a flavodoxin with flavin oxidase-like activity is required. Both class Ia and Ib RNRs have identical first coordination spheres around their metal binding sites, yet the Ia enzyme uses O2 as the oxidant, while the Ib enzyme is postulated to use HO2- as an oxidant. Both proteins can bind MnII more tightly than FeII. The importance in vivo of controlling metal delivery and avoiding protein mismetallation will be discussed.