Triosephosphate isomerase: A theoretical comparison of alternative pathways

被引：100

作者：

Cui, Q

Karplus, M ^{[1
]}

机构：

[1] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

[2] Univ Strasbourg 1, ISIS, Lab Chim Biophys, F-67000 Strasbourg, France

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2001年 / 123卷 / 10期

关键词：

D O I：

10.1021/ja002886c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Three mechanisms proposed for the triosephosphate isomerase (TIM) catalyzed reactions were studied with the QM/MM approach using B3LYP/6-31+G(d,p) as the QM method. The two pathways that involve an enediol species were found to give similar values for the barriers and the calculated rates are in satisfactory agreement with experiment. By contrast, the mechanism that involves intramolecular proton transfer in the enediolate was found to be energetically unfavorable due to electrostatic interactions with His 95, a conserved residue in TIM from different organisms. A perturbation analysis was used to determine the residues that make the major contribution to catalysis.

引用

页码：2284 / 2290

页数：7

共 43 条

[1] QUANTUM-MECHANICAL AND MOLECULAR MECHANICAL STUDIES ON A MODEL FOR THE DIHYDROXYACETONE PHOSPHATE GLYCERALDEHYDE PHOSPHATE ISOMERIZATION CATALYZED BY TRIOSEPHOSPHATE ISOMERASE (TIM) [J].