Kinetic studies of 3Dpol have shown that, like in
other polymerases, the catalytic cycle can be broadly
divided into five separate steps [22]. Within these
steps, there are typically two conformational changes
that flank phosphoryl transfer: the first positions the
NTP over the active site, and the second translocates
the nucleic acid following catalysis. The viral RNAdependent
RNA polymerases have fingers domains
that reach across the active site and are tethered to
their thumb domains, precluding large-scale fingers
domain movements that could act to reposition NTPs
for catalysis. These enzymes instead use more subtle
conformational changes to close their active sites via
a novel structural rearrangement of Motifs A and D
that are part of the palm domain [8,23]. The viral
RdRPs lack a structural analog of Tyr639 and the
fingers domain O-helix motif, making it likely that the
molecular details of the translocation mechanism
differ considerably from that of DNA-templated
polymerases.
Kinetic studies of 3Dpol have shown that, like inother polymerases, the catalytic cycle can be broadlydivided into five separate steps [22]. Within thesesteps, there are typically two conformational changesthat flank phosphoryl transfer: the first positions theNTP over the active site, and the second translocatesthe nucleic acid following catalysis. The viral RNAdependentRNA polymerases have fingers domainsthat reach across the active site and are tethered totheir thumb domains, precluding large-scale fingersdomain movements that could act to reposition NTPsfor catalysis. These enzymes instead use more subtleconformational changes to close their active sites viaa novel structural rearrangement of Motifs A and Dthat are part of the palm domain [8,23]. The viralRdRPs lack a structural analog of Tyr639 and thefingers domain O-helix motif, making it likely that themolecular details of the translocation mechanismdiffer considerably from that of DNA-templatedpolymerases.
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