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Study Points to Synonymous Mutation Effects on E. Coli Enzyme Activity

A team from Pennsylvania State University and Johns Hopkins University points to potential structural and functional consequences of synonymous mutations that alter the RNA sequence of a gene without changing the amino acid composition of the resulting protein. As they report in Nature Chemistry, the investigators tracked synonymous mutations' consequences in Escherichia coli genes coding for the type III chloramphenicol acetyltransferase, D-alanine-D-alanine ligase B, and dihydrofolate reductase enzymes, uncovering activity shifts in enzymes with synonymous mutations using multiscale modeling that took protein synthesis speed, post-translational patterns, robustness, and mechanical features into account. Along with apparent shifts in translation elongation speed, the authors point to other potential synonymous mutation effects, including possible protein misfolding. "Synonymous mutations alter translation elongation speeds and change the population of nascent chain conformations in entangled states that are near native but have lower catalytic efficiencies than that of the native state," the authors report, noting that "the specific activity — a quantity averaged over the populations of proteins in different conformational states — can increase or decrease due to synonymous mutations."