General Acid-Base Catalysis in the Mechanism of a Hepatitis Delta Virus Ribozyme
- 25 February 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 287 (5457), 1493-1497
- https://doi.org/10.1126/science.287.5457.1493
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 pK a (whereK 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 pK a perturbed to neutrality, making it “histidine-like.” Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the pK a of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.Keywords
This publication has 43 references indexed in Scilit:
- Crystallization and structure determination of a hepatitis delta virus ribozyme: use of the RNA-binding protein U1A as a crystallization module 1 1Edited by D. C. ReesJournal of Molecular Biology, 2000
- Catalytic Mechanism of Escherichia coli Glycinamide Ribonucleotide Transformylase Probed by Site-Directed Mutagenesis and pH-Dependent StudiesBiochemistry, 1999
- The Solvent-Protected Core of the Hairpin Ribozyme−Substrate ComplexBiochemistry, 1998
- Unusual Metal Ion Catalysis in an Acyl-Transferase RibozymeBiochemistry, 1998
- MECHANISTIC ASPECTS OF ENZYMATIC CATALYSIS: Lessons from Comparison of RNA and Protein EnzymesAnnual Review of Biochemistry, 1997
- Control of Memory Formation Through Regulated Expression of a CaMKII TransgeneScience, 1996
- RNAs with Dual Specificity and Dual RNAs with Similar SpecificityScience, 1994
- The MIDAS display systemJournal of Molecular Graphics, 1988
- Molecular cloning and sequencing of a human hepatitis delta (δ) virus RNANature, 1987
- pK of the lysine amino group at the active site of acetoacetate decarboxylaseBiochemistry, 1971