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TitleComprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade.
Journal, issue, pagesElife, Vol. 11, Year 2022
Publish dateSep 1, 2022
AuthorsAudrey A Burnim / Matthew A Spence / Da Xu / Colin J Jackson / Nozomi Ando /
PubMed AbstractRibonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by ...Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. Here, we structurally aligned the diverse RNR family by the conserved catalytic barrel to reconstruct the first large-scale phylogeny consisting of 6779 sequences that unites all extant classes of the RNR family and performed evo-velocity analysis to independently validate our evolutionary model. With a robust phylogeny in-hand, we uncovered a novel, phylogenetically distinct clade that is placed as ancestral to the classes I and II RNRs, which we have termed clade Ø. We employed small-angle X-ray scattering (SAXS), cryogenic-electron microscopy (cryo-EM), and AlphaFold2 to investigate a member of this clade from phage S-CBP4 and report the most minimal RNR architecture to-date. Based on our analyses, we propose an evolutionary model of diversification in the RNR family and delineate how our phylogeny can be used as a roadmap for targeted future study.
External linksElife / PubMed:36047668 / PubMed Central
MethodsEM (single particle)
Resolution3.46 Å
Structure data

EMDB-26712, PDB-7urg:
cryo-EM structure of ribonucleotide reductase from Synechococcus phage S-CBP4 bound with TTP
Method: EM (single particle) / Resolution: 3.46 Å

Chemicals

ChemComp-TTP:
THYMIDINE-5'-TRIPHOSPHATE

Source
  • synechococcus phage s-cbp4 (virus)
KeywordsOXIDOREDUCTASE / ribonucleotide reductase / Synechoccus phage / TTP

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