Substrate inhibition imposes fitness penalty at high protein stability.

ABSTRACT: Proteins are only moderately stable. It has long been debated whether this narrow range of stabilities is solely a result of neutral drift toward lower stability or purifying selection against excess stability-for which no experimental evidence was found so far-is also at work. Here, we show that mutations outside the active site in the essential Escherichia coli enzyme adenylate kinase (Adk) result in a stability-dependent increase in substrate inhibition by AMP, thereby impairing overall enzyme activity at high stability. Such inhibition caused substantial fitness defects not only in the presence of excess substrate but also under physiological conditions. In the latter case, substrate inhibition caused differential accumulation of AMP in the stationary phase for the inhibition-pr

SUBMITTER: Adkar BV 

PROVIDER: S-EPMC6561296 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature