Substitutions at a rheostat position in human aldolase A cause a shift in the conformational population.

ABSTRACT: Some protein positions play special roles in determining the magnitude of protein function: at such "rheostat" positions, varied amino acid substitutions give rise to a continuum of functional outcomes, from wild type (or enhanced), to intermediate, to loss of function. This observed range raises interesting questions about the biophysical bases by which changes at single positions have such varied outcomes. Here, we assessed variants at position 98 in human aldolase A ("I98X"). Despite being ~17 Å from the active site and far from subunit interfaces, substitutions at position 98 have rheostatic contributions to the apparent cooperativity (n_H ) associated with fructose-1,6-bisphosphate substrate binding and moderately affected binding affinity. Next, we crystallized representati

SUBMITTER: Fenton KD 

PROVIDER: S-EPMC8819835 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature