Differential effects of a mutation on the normal and promiscuous activities of orthologs: implications for natural and directed evolution.

ABSTRACT: Neutral drift occurring over millions or billions of years results in substantial sequence divergence among enzymes that catalyze the same reaction. Although natural selection maintains the primary activity of orthologous enzymes, there is, by definition, no selective pressure to maintain physiologically irrelevant promiscuous activities. Thus, the levels and the evolvabilities of promiscuous activities may vary among orthologous enzymes. Consistent with this expectation, we have found that the levels of a promiscuous activity in nine gamma-glutamyl phosphate reductase (ProA) orthologs vary by about 50-fold. Remarkably, a single amino acid change from Glu to Ala near the active site appeared to be critical for improvement of the promiscuous activity in every ortholog. The effects of this c

SUBMITTER: Khanal A 

PROVIDER: S-EPMC4271523 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature