Structural features and substrate engagement in peptide-modifying radical SAM enzymes

Area of Science:

• Biochemistry
• Enzymology
• Molecular Biology

Background:

• Ribosomally synthesized, post-translationally modified peptides (RiPPs) are biologically significant.
• Radical S-adenosylmethionine (rSAM) enzymes are a key class of bacterial enzymes that activate C-H bonds in peptides.
• These enzymes catalyze diverse chemical transformations, generating a wide array of RiPPs.

Purpose of the Study:

• To review recent advances in the field of RiPP-modifying rSAM enzymes.
• To emphasize the domain architectures and substrate engagements of these enzymes.
• To provide a comparative analysis of six structurally characterized RiPP-rSAM enzymes.

Main Methods:

• Biophysical characterizations
• Structural characterizations
• Comparative analysis of enzyme structures

Main Results:

• rSAM enzymes exhibit remarkable flexibility in accommodating large substrates.
• Distinct chemical conversions are facilitated by similar structural folds within rSAM enzymes.
• Specific domain architectures and substrate engagements influence RiPP production.

Conclusions:

• Understanding the structural basis of rSAM enzyme activity is crucial for deciphering RiPP biosynthesis.
• Linking structural elements to catalytic function provides insights into enzyme engineering.
• Harnessing the catalytic power of RiPP-rSAM enzymes has potential for broader applications.