title: Choosing the right metal: case studies of class I ribonucleotide reductases.
abstract: 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.
authors.affiliation: From the Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Huang
authors.affiliation: the Departments of Chemistry and.
authors.forename: Mackenzie J
authors.initials: MJ
authors.lastname: Parker
authors.affiliation: the Departments of Chemistry and Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 stubbe@mit.edu.
authors.forename: JoAnne
authors.initials: J
authors.lastname: Stubbe
mesh_terms: D002413:Cations, Divalent; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D002413:Cations, Divalent; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D008345:Manganese; D007501:Iron; D012264:Ribonucleotide Reductases
keywords: Bacterial Pathogenesis; Iron; Iron-Sulfur Protein; Manganese; Metal Homeostasis; Metallation; Mismetallation; Ribonucleotide Reductase; Yeast