INSIGHTS INTO CHORISMATE MUTASE CATALYSIS FROM A COMBINED QM/MM SIMULATION OF THE ENZYME REACTION

被引:144
作者
LYNE, PD
MULHOLLAND, AJ
RICHARDS, WG
机构
[1] UNIV OXFORD,OXFORD CTR MOLEC SCI,PHYS & THEORET CHEM LAB,OXFORD OX1 3QZ,ENGLAND
[2] HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138
基金
英国工程与自然科学研究理事会;
关键词
D O I
10.1021/ja00150a037
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The results from a combined QM/MM study of the reaction catalyzed by Bacillus subtilis Chorismate Mutase are presented. Chorismate Mutase catalyzes the skeletal rearrangement of chorismate to prephenate with a 2 x 10(6) rate acceleration over the solution phase reaction. Chorismate Mutase does not chemically catalyze the reaction but selectively chooses a destabilized conformer of chorismate. The simulation is consistent with previous structural studies insofar as the enzyme does not chemically catalyze the reaction. It is found that the minimum energy enzyme-substrate complex has chorismate in a distorted geometry relative to the ground state structure in the gas phase. The pyruvyl sidechain has rotated to maximize the interactions in the active site with the result that the distance between the reaction centers is shorter. In addition it is shown that the enzyme preferentially binds the transition state with the biggest interactions being due to Arg90 and Glu78. Thus the catalysis of chorismate may be rationalized in terms of a combination of substrate strain and transition state stabilization.
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页码:11345 / 11350
页数:6
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