A mechanism for the RNA‐catalyzed formation of 5′‐phosphates The origin of nucleases

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Abstract
Processes involved in RNA metabolism can be distinguished by the nature of the sugar phosphate substitution (5′ or 3′) in intermediates or products. Although it is known that 3′-phosphates are produced via a 2′,3′-cyclic phosphate intermediate, formed by nucleophilic attack on the phosphodiester bond by the adjacent 2′-OH, little is known about the production of 5′-phosphate products. We attribute 5′-phosphate intermediates and products to a preferred configuration of the pentavalent phosphorus intermediate resulting from the attack of a distant nucleophile. This intermediate is favored, since its formation is possible without major conformational changes in the molecule. Based on the two products of nucleic acid hydrolysis we define: the conjunct and disjunct nucleophile mechanisms, each of which would have independent origins. Indeed, the products of an overwhelming number of nucleases and RNases are consistent with one of these mechanistic models demontrating that the origin of these enzymes are deeply rooted in the intrinsic chemistry of phosphate esters.