A. Roth et Rr. Breaker, AN AMINO-ACID AS A COFACTOR FOR A CATALYTIC POLYNUCLEOTIDE, Proceedings of the National Academy of Sciences of the United Statesof America, 95(11), 1998, pp. 6027-6031
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.