General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme

Shu Ichi Nakano, Durga M. Chadalavada, Philip C. Bevilacqua

Research output: Contribution to journalArticlepeer-review

378 Scopus citations


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) (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 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.

Original languageEnglish (US)
Pages (from-to)1493-1497
Number of pages5
Issue number5457
StatePublished - Feb 25 2000

All Science Journal Classification (ASJC) codes

  • General


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