Choosing the Right Metal: Case Studies of Class I Ribonucleotide Reductases [Microbiology]

August 26th, 2014 by Huang, M., Parker, M. J., Stubbe, J.

Over one-third of all proteins require metallation for function (Waldron, K.J., Rutherford, J.C.; Ford, D.; Robinson, N.J. (2009) Nature 460, 823-830). As biochemical studies of most proteins depend on their isolation subsequent to recombinant expression (i.e. they are seldom purified from their host organism), there is no gold standard to assess faithful metallo-cofactor assembly and associated function. The biosynthetic machinery for metallo-cofactor formation in the recombinant expression system may be absent, inadequately expressed, or incompatible with a heterologously expressed protein. A combination of biochemical and genetic studies has led to the identification of key proteins involved in biosynthesis and likely repair of the metallo-cofactor of ribonucleotide reductases in both bacteria and the budding yeast. In this minireview, we will discuss the recent progress in understanding controlled delivery of metal, oxidants, and reducing equivalents for cofactor assembly in ribonucleotide reductases and highlight issues associated with controlling Fe/Mn metallation and avoidance of mismetallation.