Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States.
Curr Opin Struct Biol. 2009 Dec;19(6):768-74. doi: 10.1016/j.sbi.2009.10.012. Epub 2009 Nov 10.
The structural basis for nucleotide incorporation fidelity remains an open question for all nucleic acid polymerases. Addressing this question for the viral RNA-dependent RNA polymerase (RdRp) is of particular, practical significance because it is a determinant of sensitivity to antiviral nucleosides and may be a determinant of viral virulence. All polymerases are thought to employ the same catalytic mechanism, but the rate of nucleotide incorporation can vary substantially. Here we review some of the recent work with the RdRp that leads us to suggest that structure provides only a partial understanding of RdRp function and dynamics may be the missing link.
核苷酸掺入保真度的结构基础仍然是所有核酸聚合酶的一个悬而未决的问题。解决这个问题对于依赖病毒 RNA 的 RNA 聚合酶(RdRp)具有特殊的实际意义,因为它是决定对抗病毒核苷敏感性的因素,并且可能是决定病毒毒力的因素。所有聚合酶都被认为采用相同的催化机制,但核苷酸掺入的速率可能有很大差异。在这里,我们回顾了一些与 RdRp 相关的最新工作,这些工作使我们提出这样的观点,即结构仅提供了对 RdRp 功能的部分理解,而动态可能是缺失的环节。