First, investigators have produced a diverse array of ribozymes that catalyze fundamental metabolic reactions and bind specific ligands. However, new research establishes the homology of all RNRs and places their biochemistry beyond the plausible scope of ribozyme catalysis, a view corroborated by the distribution of catalytic and functional RNA found within cells. Two aspects of RNR-catalyzed reduction inform the relative timing of DNA evolution. Active sites and proposed reaction mechanisms in DNA biosynthesis. The orange lines indicate the enzyme, with important residues shown in yellow.
Chemical structures represent substrates.
Red dots indicate free radicals. Only two cysteine residues are used, the cysteine radical is generated from a glycyl radical further along the protein, and formate is reduced to carbon dioxide and water during the reaction. That the extraordinary sulfur-based chemistry of RNRs has been absolutely conserved, despite divergence in nearly every other aspect of the enzymes, implies that nature has only discovered this one mechanism for ribose reduction. Perhaps no others are biologically feasible or accessible. Two further ways in which DNA could exist in an RNA world without proteins deserve consideration.