General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme.
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.
Nakano
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Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Chadalavada
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Bevilacqua
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D020029:Base Pairing; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D003035:Cobalt / Q000378:metabolism; D018360:Crystallography, X-Ray; D003698:Hepatitis Delta Virus / Q000737:chemistry* / Q000201:enzymology; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011522:Protons; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
D008670:Metals; D011522:Protons; D016337:RNA, Catalytic; D012367:RNA, Viral; C030862:cobalt ammonium complex; D003035:Cobalt; D008274:Magnesium; D002118:Calcium