Transesterification thio effects of phosphate diesters: Free energy barriers and kinetic and equilibrium isotope effects from density-functional theory

被引:59
作者
Liu, Yun
Gregersen, Brent A.
Hengge, Alvan
York, Darrin M.
机构
[1] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA
[2] Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA
关键词
D O I
10.1021/bi060869f
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:10043 / 10053
页数:11
相关论文
共 98 条
[1]   Canonical variational theory for enzyme kinetics with the protein mean force and multidimensional quantum mechanical tunneling dynamics.: Theory and application to liver alcohol dehydrogenase [J].
Alhambra, C ;
Corchado, J ;
Sánchez, ML ;
Garcia-Viloca, M ;
Gao, J ;
Truhlar, DG .
JOURNAL OF PHYSICAL CHEMISTRY B, 2001, 105 (45) :11326-11340
[2]   INTRAMOLECULAR TRANSESTERIFICATION IN THIOPHOSPHATE-ANALOGS OF AN RNA-DIMER [J].
ALMER, H ;
STROMBERG, R .
TETRAHEDRON LETTERS, 1991, 32 (30) :3723-3726
[3]   Base catalysis and leaving group dependence in intramolecular alcoholysis of uridine 3'-(aryl phosphorothioate)s [J].
Almer, H ;
Stromberg, R .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (34) :7921-7928
[4]   Mechanistic alternatives phosphate monoester hydrolysis:: what conclusions can be drawn from available experimental data? [J].
Åqvist, J ;
Kolmodin, K ;
Florian, J ;
Warshel, A .
CHEMISTRY & BIOLOGY, 1999, 6 (03) :R71-R80
[5]   Thiolysis and alcoholysis of phosphate tri- and monoesters with alkyl and aryl leaving groups. An ab initio study in the gas phase [J].
Arantes, GM ;
Chaimovich, H .
JOURNAL OF PHYSICAL CHEMISTRY A, 2005, 109 (25) :5625-5635
[6]   Theoretical modelling of kinetic isotope effects for glycoside hydrolysis in aqueous solution by a hybrid quantum-mechanical molecular-mechanical method [J].
Barnes, JA ;
Williams, IH .
CHEMICAL COMMUNICATIONS, 1996, (02) :193-194
[7]   A new definition of cavities for the computation of solvation free energies by the polarizable continuum model [J].
Barone, V ;
Cossi, M ;
Tomasi, J .
JOURNAL OF CHEMICAL PHYSICS, 1997, 107 (08) :3210-3221
[8]   Stability analysis for solutions of the closed shell Kohn-Sham equation [J].
Bauernschmitt, R ;
Ahlrichs, R .
JOURNAL OF CHEMICAL PHYSICS, 1996, 104 (22) :9047-9052
[9]   DENSITY-FUNCTIONAL THERMOCHEMISTRY .3. THE ROLE OF EXACT EXCHANGE [J].
BECKE, AD .
JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (07) :5648-5652
[10]   CALCULATION OF EQUILIBRIUM CONSTANTS FOR ISOTOPIC EXCHANGE REACTIONS [J].
BIGELEISEN, J ;
MAYER, MG .
JOURNAL OF CHEMICAL PHYSICS, 1947, 15 (05) :261-267