title: Altered (transition) states: mechanisms of solution and enzyme catalyzed RNA 2'-O-transphosphorylation.
abstract: Although there have been great strides in defining the mechanisms of RNA strand cleavage by 2'-O-transphosphorylation, long-standing questions remain. How do different catalytic modes such as acid/base and metal ion catalysis influence transition state charge distribution? Does the large rate enhancement characteristic of biological catalysis result in different transition states relative to solution reactions? Answering these questions is important for understanding biological catalysis in general, and revealing principles for designing small molecule inhibitors. Recent application of linear free energy relationships and kinetic isotope effects together with multi-scale computational simulations are providing tentative answers to these questions for this fundamentally important class of phosphoryl transfer reactions.
authors.affiliation: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kellerman
authors.affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, NJ, United States.
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
authors.affiliation: Department of Biochemistry & Molecular Biology, and Chemistry, University of Chicago, Chicago, IL, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
authors.affiliation: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, United States. Electronic address: meh2@case.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Harris
mesh_terms: D055162:Biocatalysis; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010766:Phosphorylation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D012996:Solutions
chemical_list: D004798:Enzymes; D012996:Solutions; D012313:RNA