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The hepatitis delta virus (HDV) ribozyme uses both metal ion and nucleobase catalysis in its cleavage mechanism. A reverse G·U wobble was observed in a recent crystal structure of the precleaved state. This unusual base pair positions a Mg(2+) ion to participate in catalysis. Herein, we used molecular dynamics (MD) and X-ray crystallography to characterize(More)
The hepatitis delta virus (HDV) ribozyme self-cleaves in the presence of a wide range of monovalent and divalent ions. Prior theoretical studies provided evidence that self-cleavage proceeds via a concerted or stepwise pathway, with the outcome dictated by the valency of the metal ion. In the present study, we measure stereospecific thio effects at the(More)
The hepatitis delta virus ribozyme catalyzes an RNA cleavage reaction using a catalytic nucleobase and a divalent metal ion. The catalytic base, C75, serves as a general acid and has a pK(a) shifted toward neutrality. Less is known about the role of metal ions in the mechanism. A recent crystal structure of the precleavage ribozyme identified a Mg²⁺ ion(More)
The crystal structure of the precleaved form of the hepatitis delta virus (HDV) ribozyme reveals two G•U wobbles near the active site: a rare reverse G•U wobble involving a syn G base, and a standard G•U wobble at the cleavage site. The catalytic mechanism for this ribozyme has been proposed to involve a Mg(2+) ion bound to the reverse G•U wobble, as well(More)
The hepatitis delta virus (HDV) ribozyme catalyzes a self-cleavage reaction using a combination of nucleobase and metal ion catalysis. Both divalent and monovalent ions can catalyze this reaction, although the rate is slower with monovalent ions alone. Herein, we use quantum mechanical/molecular mechanical (QM/MM) free energy simulations to investigate the(More)
Metal ion and nucleobase catalysis are important for ribozyme mechanism, but the extent to which they cooperate is unclear. A crystal structure of the hepatitis delta virus (HDV) ribozyme suggested that the pro-RP oxygen at the scissile phosphate directly coordinates a catalytic Mg(2+) ion and is within hydrogen bonding distance of the amine of the general(More)
A recent crystal structure of the precleaved HDV ribozyme along with biochemical data support a mechanism for phosphodiester bond self-cleavage in which C75 acts as a general acid and bound Mg(2+) ion acts as a Lewis acid. Herein this precleaved crystal structure is used as the basis for quantum mechanical/molecular mechanical calculations. These(More)
The glmS ribozyme catalyzes a self-cleavage reaction at the phosphodiester bond between residues A-1 and G1. This reaction is thought to occur by an acid-base mechanism involving the glucosamine-6-phosphate cofactor and G40 residue. Herein quantum mechanical/molecular mechanical free energy simulations and pKa calculations, as well as experimental(More)
Metropolis Monte Carlo simulations on the square-shoulder fluid of Malescio and Pellicane are used to trace the temperature dependent excess entropy, the heat capacity, and configurational energy along several isochores, including those for which mechanically stable zero-temperature structures have been predicted. Thermodynamic signatures of structural(More)