title: Class I ribonucleotide reductases: metallocofactor assembly and repair in vitro and in vivo.
abstract: Incorporation of metallocofactors essential for the activity of many enyzmes is a major mechanism of posttranslational modification. The cellular machinery required for these processes in the case of mono- and dinuclear nonheme iron and manganese cofactors has remained largely elusive. In addition, many metallocofactors can be converted to inactive forms, and pathways for their repair have recently come to light. The class I ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides and require dinuclear metal clusters for activity: an Fe(III)Fe(III)-tyrosyl radical (Y•) cofactor (class Ia), a Mn(III)Mn(III)-Y• cofactor (class Ib), and a Mn(IV)Fe(III) cofactor (class Ic). The class Ia, Ib, and Ic RNRs are structurally homologous and contain almost identical metal coordination sites. Recent progress in our understanding of the mechanisms by which the cofactor of each of these RNRs is generated in vitro and in vivo and by which the damaged cofactors are repaired is providing insight into how nature prevents mismetallation and orchestrates active cluster formation in high yields.
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. jcotruvo@mit.edu
authors: Joseph A
authors: JA
authors: Cotruvo
authors: Joanne
authors: J
authors: Stubbe
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003067:Coenzymes / Q000737:chemistry* / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015204:Spectroscopy, Mossbauer
chemical_list: D001426:Bacterial Proteins; D003067:Coenzymes; D005656:Fungal Proteins; D008670:Metals; D012264:Ribonucleotide Reductases