Natural and Synthetic Suppressor Mutations Defy Stability–Activity Tradeoffs

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.

• Publication year

  2022

• Venue

  Biochemistry

• Publication date

  2022-02-10

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/acs.biochem.1c00805PMID 35142509PMCID 8893143
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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