Affiliation:
1. Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Abstract
Many protein enzymes use general acid-base catalysis as a way to increase reaction rates. The amino acid histidine is optimized for this function because it has a p
K
a
(where
K
a
is the acid dissociation constant) near physiological pH. The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond. Reactivity-pH profiles in monovalent or divalent cations, as well as distance to the leaving-group oxygen, implicate cytosine 75 (C75) of the ribozyme as the general acid and ribozyme-bound hydrated metal hydroxide as the general base in the self-cleavage reaction. Moreover, C75 has a p
K
a
perturbed to neutrality, making it “histidine-like.” Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the p
K
a
of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.
Publisher
American Association for the Advancement of Science (AAAS)
Reference62 articles.
1. T. R. Cech and B. L. Golden in The RNA World R. F. Gesteland T. R. Cech J. F. Atkins Eds. (Cold Spring Harbor Laboratory Press Cold Spring Harbor NY ed. 2 1999) pp. 321–349.
2. Narlikar G. J., Herschlag D., Annu. Rev. Biochem. 66, 19 (1997).
3. Jencks W. P., Adv. Enzymol. 43, 219 (1975).
4. Piccirilli J. A., Vyle J. S., Caruthers M. H., Cech T. R., Nature 361, 85 (1993);
5. Weinstein L. B., Jones B. C., Cosstick R., Cech T. R., Nature 388, 805 (1997) ;
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374 articles.
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