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289 The role of metal ions in RNA catalysis Martha J Fedor Understanding the catalytic mechanisms of RNA enzymes remains In principle, enzymes could use a variety of strategies to an important and intriguing challenge — one that has grown in accelerate phosphodiester transesterification reactions, importance since the recent demonstration that the ribosome is a including the positioning and orientation of reactive groups, ribozyme. At first, it seemed that all RNA enzymes compensate for general acid/base catalysis, electrostatic stabilization of the limited chemical versatility of ribonucleotide functional groups negative charge in the transition state or destabilization of by recruiting obligatory metal ion cofactors to carry out catalytic the ground state [2,3]. Like their protein counterparts, RNA chemistry. Mechanistic studies of the large self-splicing and enzymes can fold into compact, ordered structures with pre-tRNA-processing ribozymes continue to support this idea, precisely positioned functional groups, as illustrated beauti yielding increasingly detailed views of RNA active sites as fully in recent crystal structures [4,5,6••,7]. In contrast to scaffolds for positioning catalytic metal ions. Re-evaluation of the amino acids that make up protein enzyme active sites, the methodologies used to distinguish catalytic and structural however, functional groups of ribonucleosides undergo roles for metal ions, however, has challenged this notion in the significant ionization only below pH 5 and above pH 9, case of the small self-cleaving RNAs. Recent studies of the small which would seem to make them unable