JoAnne Stubbe, Massachusetts Institute of Technology, "Assembly of the diferric and dimanganese-tyrosyl radical cofactors essential in the class Ia and Ib ribonucleotide reductases"

Nov 30 2010, 11:00 am
Distinguished Lecture Series Guest Speaker: 

JoAnne Stubbe

Novartis Professor of Chemistry, Massachusetts Institute of Technology
Professor of Biology, Massachusetts Institute of Technology

Date & Time: 
Tuesday, November 30, 2010, 11:00AM
Location: 
Klaus 1116E
Host: 
Jeffrey Skolnick
Abstract: 
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.
Additional Info: 

Congratulations to Dr. Stubbe for winning the National Medal of Science!

Dr. Stubbe's General Research Interests:

  • Mechanism of natural product DNA Cleavers used clinically: our interests include: 2D NMR methods to determine the structures of the drugs bound to DNA, synthesis and structure of the deoxyribose lesions generated by the drugs and mechanism of repair of these lesions
  • Mechanism and Regulation of Ribonucleotide Ruductases: our interests include study of clinically active compounds that inactivate reductases; Mechanism of metallo-cofactor assembly in vivo; mechanism of radical initiation using technology to insert unnatural amino acids into the proteins; signal transduction cascades induced by DNA damaging agents;
  • Polyester Biosynthesis: understanding non-template driven polymerization reactions and use of bioengineering methods to generate new biodegradable polymers;
  • Mechanism, Structure, and Regulation of the Purine Biosynthetic Pathway: studies to understand the importance of transient protein-protein interactions in vivo.

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