Dynamics: the missing link between structure and function of the viral RNA-dependent RNA polymerase?
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.
Cameron
Craig E
CE
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States. cec9@psu.edu
Moustafa
Ibrahim M
IM
Arnold
Jamie J
JJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D020134:Catalytic Domain; D006801:Humans; D009711:Nucleotides / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014780:Viruses / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism
D000998:Antiviral Agents; D009711:Nucleotides; D012324:RNA-Dependent RNA Polymerase