NUCLEIC ACID-BINDING METABOLIC ENZYMES - LIVING FOSSILS OF STEREOCHEMICAL INTERACTIONS

Recently, a series of intriguing observations expanded the List of a n umber of metabolic enzymes known to be associated with various forms o f nucleic acids, including single- and double-stranded DNA, cognate an d noncognate RNAs, and specific tRNAs. There is no clear reason why su ch 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 dist ribution and their participation in fundamental biochemical pathways, it appears that these enzymes do not share any structural or functiona l characteristics. Given that most of these proteins require nucleotid e-based cofactors for their activity, it is proposed that they may rep resent genuine molecular fossils of the transition from an RNA to a pr otein 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 pro teins and their nucleic acid substrates remains unclear, but it may re present an extended form of stereochemical interactions that have been proposed for the origins of the genetic code.