Structural dynamics shape the fitness window of alanine:glyoxylate aminotransferase.

ABSTRACT: The conformational landscape of a protein is constantly expanded by genetic variations that have a minimal impact on the function(s) while causing subtle effects on protein structure. The wider the conformational space sampled by these variants, the higher the probabilities to adapt to changes in environmental conditions. However, the probability that a single mutation may result in a pathogenic phenotype also increases. Here we present a paradigmatic example of how protein evolution balances structural stability and dynamics to maximize protein adaptability and preserve protein fitness. We took advantage of known genetic variations of human alanine:glyoxylate aminotransferase (AGT1), which is present as a common major allelic form (AGT-Ma) and a minor polymorphic form (AGT-Mi) expressed i

SUBMITTER: Dindo M 

PROVIDER: S-EPMC8996469 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature