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Structure-function relationships underlying the replication fidelity of viral RNA-dependent RNA polymerases.


ABSTRACT:

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Viral RNA-dependent RNA polymerases are considered to be low-fidelity enzymes, providing high mutation rates that allow for the rapid adaptation of RNA viruses to different host cell environments. Fidelity is tuned to provide the proper balance of virus replication rates, pathogenesis, and tissue tropism needed for virus growth. Using our structures of picornaviral polymerase-RNA elongation complexes, we have previously engineered more than a dozen coxsackievirus B3 polymerase mutations that significantly altered virus replication rates and in vivo fidelity and also provided a set of secondary adaptation mutations after tissue culture passage. Here we report a biochemical analysis of these mutations based on rapid stopped-flow kinetics to determine elongation rates and n

SUBMITTER: Campagnola G 

PROVIDER: S-EPMC4301111 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature