Structural Basis for a Scaffolding Role of the COM Domain in Nonribosomal Peptide Synthetases.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are multi-domain enzymes that catalyze the biosynthesis of therapeutically relevant natural products. Efficient peptide synthesis relies on intricate domain interactions, whose underlying principles remain poorly understood. The communication-mediating (COM) domains facilitate interactions between separate NRPS subunits. For unknown reasons, COM domains co-occur with epimerization (E) domains, are partially embedded within the adjacent condensation (C) domains and can also be found as internal cis-COM domains. These features set COM domains apart from other docking domains. We present the first crystal structure of a cis-COM domain within an E-COM-C domain arrangement from modules 4 and 5 of bacitracin synthetase 3 (BacC). The structure reveals a co

SUBMITTER: Diecker J 

PROVIDER: S-EPMC12402864 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature