Transition State Analysis of Model and Enzymatic Prenylation Reactions

摘要

We present here a TS structure for the reaction catalyzed by PFTase that complements X-ray crystallographic studies and provides a clear structural framework for understanding the results of previous mechanistic investigations of this enzyme, including stereochemical and kinetic analyses. The experiments reported here provide powerful insights into an important class of biological reactions through a combination of model chemistry, computation, and kinetic analysis. Finally, it should be noted that the KIE analysis described here was accomplished through experiments performed with stable isotopes and did not require radiolabeled compounds. It is likely that the role of ESI-MS and NMR in KIE analyses of biological processes will continue to grow in the future.