Networks of noncovalent interactions are important for protein structural dynamics. We used nuclear magnetic resonance chemical shift covariance analyses on an inactive variant of the alpha subunit of tryptophan synthase to map amino acid interaction networks across its catalytic cycle. Although some network connections were common to every enzyme state, many of the network connections strengthened or weakened over the catalytic cycle; these changes were highly coordinated. These results suggest a higher level of network organization. Our analyses identified periodic, second-order networks that show highly coordinated interaction changes across the catalytic cycle. These periodic networks may help synchronize the sequence of structural transitions necessary for enzyme function. Molecular dynamics simulations identified interaction changes across the catalytic cycle, including those involving the catalytic residue Glu49, which may help drive other interaction changes throughout the enzyme structure. Similar periodic networks may direct structural transitions and allosteric interactions in other proteins. Amino acid interaction networks are proposed to be important for protein function and regulation. O'Rourke et al. identified networks that change cooperatively and coordinately with the catalytic cycle of alpha tryptophan synthase. Such networks likely drive the protein through functionally important structural states, and help synchronize function with the beta subunit.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology