Coordinated Network Changes Across the Catalytic Cycle of Alpha Tryptophan Synthase

Abstract

Networks of noncovalent interactions play important roles in the structural dynamics of globular proteins. Allosteric signals can propagate from the surface of an enzyme into its active site through these amino acid interaction networks. We used nuclear magnetic resonance chemical shift covariance analyses on a catalytically inactive variant of the alpha subunit of tryptophan synthase to map its amino acid interaction networks across its entire catalytic cycle. Each enzyme intermediate has unique sets of residues that display high chemical shift correlations across a set of alanine-to-glycine loop substitutions. Moreover, these chemical shift correlations systematically increase or decrease as a function of the catalytic cycle. These studies indicate that the enzyme intermediates have different amino acid interaction networks, and these network transitions are likely important for catalytic cycle progression. The different network interactions likely help to position catalytic machinery and coordinate function with the beta subunit.