Nucleic acid-binding metabolic enzymes: living fossils of stereochemical interactions?

Recently, a series of intriguing observations expanded the list of a number of metabolic enzymes known to be associated with various forms of nucleic acids, including single- and double-stranded DNA, cognate and noncognate RNAs, and specific tRNAs. There is no clear reason why such a phenomenon should take place in contemporary cell physiology, or, further, why such a property has evolved at all. Sixteen known cases are presented in an attempt to delineate any common features of these enzymes. Apart from their ancient nature, as judged by their wide distribution and their participation in fundamental biochemical pathways, it appears that these enzymes do not share any structural or functional characteristics. Given that most of these proteins require nucleotide-based cofactors for their activity, it is proposed that they may represent genuine molecular fossils of the transition from an RNA to a protein world. Their nucleic acid-binding properties are in keeping with previously proposed hypotheses regarding the origins and evolution of nucleotide-based cofactors. The mode of interaction between these proteins and their nucleic acid substrates remains unclear, but it may represent an extended form of stereochemical interactions that have been proposed for the origins of the genetic code.