Catalytic Site Proximity Profiling for Functional Unification of Sequence-Diverse Radical <i>S</i>-Adenosylmethionine Enzymes.

ABSTRACT: The radical S-adenosylmethionine (rSAM) superfamily has become a wellspring for discovering new enzyme chemistry, especially regarding ribosomally synthesized and post-translationally modified peptides (RiPPs). Here, we report a compendium of nearly 15,000 rSAM proteins with high-confidence involvement in RiPP biosynthesis. While recent bioinformatics advances have unveiled the broad sequence space covered by rSAM proteins, the significant challenge of functional annotation remains unsolved. Through a combination of sequence analysis and protein structural predictions, we identified a set of catalytic site proximity residues with functional predictive power, especially among the diverse rSAM proteins that form sulfur-to-α carbon thioether (sactionine) linkages. As a case study, we r

SUBMITTER: Precord TW 

PROVIDER: S-EPMC10288494 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature