Energy considerations show that low-barrier hydrogen bonds do not offer a catalytic advantage over ordinary hydrogen bonds

被引:182
作者
Warshel, A
Papazyan, A
机构
[1] Department of Chemistry, University of Southern California, Los Angeles
关键词
enzymes; transition state; subtilisin; electrostatics; evolution;
D O I
10.1073/pnas.93.24.13665
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Low-barrier hydrogen bonds have recently been proposed as a major factor in enzyme catalysis. Here we evaluate the feasibility of transition state (TS) stabilization by low-barrier hydrogen bonds in enzymes. Our analysis focuses on the facts that (i) a low-barrier hydrogen bond is less stable than a regular hydrogen bond in water, (ii) TSs are more stable in the enzyme active sites than in eater, and (iii) a nonpolar active site would destabilize the TS relative to its energy in water. Combining these points and other experimental and theoretical facts in a physically consistent framework shows that a low-barrier hydrogen bond cannot stabilize the TS more than an ordinary hydrogen bond. The reason for the large catalytic effect of active site hydrogen bonds is that their formation entails a lower reorganization energy than their solution counterparts, due to the preorganized enzyme environment.
引用
收藏
页码:13665 / 13670
页数:6
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