Johnson K A
Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802.
Philos Trans R Soc Lond B Biol Sci. 1992 Apr 29;336(1276):107-12. doi: 10.1098/rstb.1992.0050.
The extraordinary fidelity of DNA replication during forward polymerization and exonuclease error correction is largely a function of a conformational change that occurs in response to a correct dNTP binding to properly base-paired duplex DNA. The conformational change serves as a kinetic barrier to effect the rapid incorporation of correct bases while minimizing the rate of polymerization with incorrect bases and allowing for selective removal of mismatches. However, in spite of the number of attractive features to the conformational change model, the evidence in support of such a rate-limiting step is still subject to significant uncertainty. It is the challenge of further work on DNA polymerases as well as many other enzyme systems to devise new methods to define the transient state of the enzyme during catalysis and to relate the kinetic and thermodynamic parameters to the enzyme structure.
在正向聚合和核酸外切酶纠错过程中，DNA复制的极高保真度很大程度上是一种构象变化的结果，这种构象变化是对正确的脱氧核糖核苷三磷酸（dNTP）与正确碱基配对的双链DNA结合作出的反应。这种构象变化充当了一种动力学屏障，以实现正确碱基的快速掺入，同时将与错误碱基聚合的速率降至最低，并允许选择性去除错配。然而，尽管构象变化模型有诸多吸引人的特性，但支持这种限速步骤的证据仍存在很大不确定性。这是进一步研究DNA聚合酶以及许多其他酶系统面临的挑战，即设计新方法来定义酶在催化过程中的瞬态，并将动力学和热力学参数与酶结构联系起来。
