Choosing the right metal: case studies of class I ribonucleotide reductases.
Over one-third of all proteins require metallation for function (Waldron, K. J., Rutherford, J. C., Ford, D., and 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 metallocofactor assembly and associated function. The biosynthetic machinery for metallocofactor 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 metallocofactor 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.
['Huang|Mingxia|M|', 'Parker|Mackenzie J|MJ|', 'Stubbe|JoAnne|J|']
D002413:Cations, Divalent D004926:Escherichia coli D029968:Escherichia coli Proteins D015870:Gene Expression D007501:Iron D008345:Manganese D008958:Models, Molecular D011994:Recombinant Proteins D012264:Ribonucleotide Reductases D012441:Saccharomyces cerevisiae D029701:Saccharomyces cerevisiae Proteins D013045:Species Specificity D013329:Structure-Activity Relationship
Metallation Ribonucleotide Reductase Yeast Mismetallation Bacterial Pathogenesis Iron Iron-Sulfur Protein Manganese Metal Homeostasis