Transesterification Thio Effects of Phosphate Diesters: Free Energy Barriers and Kinetic and Equilibrium Isotope Effects from Density-Functional Theory

Authors

Yun Liu
Brent A. Gregersen
Alvan C. Hengge, Utah State UniversityFollow
Darrin M. York

Document Type

Article

Journal/Book Title

Biochemistry

Publication Date

2006

Volume

45

Issue

33

First Page

10043

Last Page

10053

Abstract

Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the in-line dianionic methanolysis of the native (unsubstituted) and thio-substituted cyclic phosphates. These reactions represent reverse reaction models for RNA transesterification under alkaline conditions. The effect of solvent is treated with explicit (single and double) water molecules and self-consistently with an implicit (continuum) solvation model. Singly substituted reactions at the nonbridging O_P1 position and bridging O_2‘, O_3‘, and O_5‘ positions and a doubly substituted reaction at the O_P1 and O_P2 positions were considered. Aqueous free energy barriers are calculated, and the structures and bond orders of the rate-controlling transition states are characterized. The results are consistent with available experimental data and provide useful information for the interpretation of measured isotope and thio effects used to probe mechanism in phosphoryl transfer reactions catalyzed by enzymes and ribozymes

Recommended Citation

Y. Liu, B. A. Gregersen, A. C. Hengge and D. M. York. “Transesterification Thio Effects of Phosphate Diesters: Free Energy Barriers and Kinetic and Equilibrium Isotope Effects from Density-Functional Theory.” Biochemistry;2006; 45(33); 10043-10053.