AN AMINO-ACID AS A COFACTOR FOR A CATALYTIC POLYNUCLEOTIDE

Natural ribozymes require metal ion cofactors that aid both in structu ral folding and in chemical catalysis. contrast, many protein enzymes produce dramatic rate enhancements using only the chemical groups that are supplied by their constituent amino acids. This fact is widely vi ewed as the most important feature that makes protein a superior polym er for the construction of biological catalysts. Herein we report the in vitro selection of a catalytic DNA that uses histidine as an active component for an RNA cleavage reaction. An optimized deoxyribozyme fr om this selection requires L-histidine or a closely related analog to catalyze RNA phosphoester cleavage, producing a rate enhancement of ap proximate to 1-million-fold over the rate of substrate cleavage in the absence of enzyme. Kinetic analysis indicates that a DNA-histidine co mplex may perform a reaction that is analogous to the first step of th e proposed catalytic mechanism of RNase A, in which the imidazole grou p of histidine serves as a general base catalyst. Similarly, ribozymes of the ''RNA world'' may have used amino acids and other small organi c cofactors to expand their otherwise limited catalytic potential.