Absolute Stereochemistry of the Second Step of Ribonuclease Action

Abstract

PANCREATIC ribonuclease catalyses the decomposition of a ribonucleic acid by a two-step mechanism: a transesterification followed by hydrolysis of the resulting cyclic phosphate¹. The various mechanisms suggested can be classified as either “in-line” or “adjacent” depending on the relative geometry of the incoming and outgoing groups during the displacement reaction² (Fig. 1). In particular, any simple mechanism in which it is assumed that the same group acts first as a general base toward the attacking nucleophile, then as a general acid toward the leaving group, implies an adjacent geometry. The alternative, in which there is a considerable movement of either the catalytic group or the substrate, is unlikely. The two steps may, however, have different mechanisms according to this criterion without violating microscopic reversibility, for a nucleoside is obviously not necessarily equivalent to a water molecule³.