6tqw | pdb_00006tqw
Crystal structure of ribonucleotide reductase NrdF from Bacillus anthracis anaerobically soaked with Fe(II) and Mn(II) ions
Structural highlights
FunctionQ81TB4_BACAN Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.[PIRNR:PIRNR000355] Publication Abstract from PubMedCorrect protein metallation in the complex mixture of the cell is a prerequisite for metalloprotein function. While some metals, such as Cu, are commonly chaperoned, specificity towards metals earlier in the Irving-Williams series is achieved through other means, the determinants of which are poorly understood. The dimetal carboxylate family of proteins provides an intriguing example, as different proteins, while sharing a common fold and the same 4-carboxylate 2-histidine coordination sphere, are known to require either a Fe/Fe, Mn/Fe or Mn/Mn cofactor for function. We previously showed that the R2lox proteins from this family spontaneously assemble the heterodinuclear Mn/Fe cofactor. Here we show that the class Ib ribonucleotide reductase R2 protein from Bacillus anthracis spontaneously assembles a Mn/Mn cofactor in vitro, under both aerobic and anoxic conditions, when the metal-free protein is subjected to incubation with Mn(II) and Fe(II) in equal concentrations. This observation provides an example of a protein scaffold intrinsically predisposed to defy the Irving-Williams series and supports the assumption that the Mn/Mn cofactor is the biologically relevant cofactor in vivo. Substitution of a second coordination sphere residue changes the spontaneous metallation of the protein to predominantly form a heterodinuclear Mn/Fe cofactor under aerobic conditions and a Mn/Mn metal center under anoxic conditions. Together, the results describe the intrinsic metal specificity of class Ib RNR and provide insight into control mechanisms for protein metallation. The Bacillus anthracis class Ib ribonucleotide reductase subunit NrdF intrinsically selects manganese over iron.,Grave K, Griese JJ, Berggren G, Bennett MD, Hogbom M J Biol Inorg Chem. 2020 Apr 15. pii: 10.1007/s00775-020-01782-3. doi:, 10.1007/s00775-020-01782-3. PMID:32296998[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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