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Natural and Synthetic Suppressor Mutations Defy Stability–Activity Tradeoffs

Year: 2022

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Thermodynamic stability represents one important constraint on protein evolution, but the molecular basis for how mutations that change stability impact fitness remains unclear. Here, we demonstrate that a prevalent global suppressor mutation in TEM β-lactamase, M182T, increases fitness by reducing proteolysis in vivo . We also show that a synthetic mutation, M182S, can act as a global suppressor and suggest that its absence from natural populations is due to genetic inaccessibility rather than fundamental differences in the protein’s stability or activity.

Source: Biochemistry

DOI: 10.1021/acs.biochem.1c00805