4dr0

Publication Abstract from PubMed

Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn^III₂-Y*, in their homodimeric NrdF (beta2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn^II₂ form of NrdF is an important component in understanding O₂ -mediated formation of the active metallocofactor, a subject of much interest since a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is that of <i>Escherichia coli</i> Mn^II₂-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 A resolution crystal structure of <i>Bacillus subtilis</i> Mn^II₂-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus genera. The structures of the metal clusters in the beta2 dimer are distinct from those observed in <i>E. coli</i> Mn^II₂-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn^II₂ cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn^III₂-Y* cofactor assembly in class Ib RNRs.

The dimanganese(II) site in <i>Bacillus subtilis</i> class Ib ribonucleotide reductase.,Boal AK, Cotruvo JA, Stubbe J, Rosenzweig AC Biochemistry. 2012 Mar 23. PMID:22443445^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.