The depth of chemical time and the power of enzymes as catalysts

被引:732
作者
Wolfenden, R [1 ]
Snider, MJ [1 ]
机构
[1] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
关键词
D O I
10.1021/ar000058i
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The fastest known reactions include reactions catalyzed by enzymes, but the rate enhancements that enzymes produce had not been fully appreciated until recently. In the absence of enzymes, these same reactions are among the slowest that have ever been measured, some with half-times approaching the age of the Earth. This difference provides a measure of the proficiencies of enzymes as catalysts and their relative Susceptibilities to inhibition by transition-state analogue inhibitors. Thermodynamic comparison,, bem,een spontaneous and enzyme-catalyzed reactions, Coupled with structural information. suggest that in addition to electrostatic and H-bonding interactions, the liberation of water molecules from an enzyme's active site into bulk solvent sometimes plays a prominent role in determining the relative binding affinities of the altered substrate in the ground state and transition state. These comparisons also indicate a high level of synergism in the action of binding determinants of both the substrate and the enzyme, that are not directly involved in the chemical transformation of the substrate but contribute to the rate of its transformation at an enzyme's active site.
引用
收藏
页码:938 / 945
页数:8
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