Altered (transition) states: mechanisms of solution and enzyme catalyzed RNA 2 '-O-transphosphorylation

作者:Kellerman Daniel L; York Darrin M; Piccirilli Joseph A; Harris Michael E*
来源:Current Opinion in Chemical Biology, 2014, 21: 96-102.
DOI:10.1016/j.cbpa.2014.06.010

摘要

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.

  • 出版日期2014-8
  • 单位rutgers