Intermediary conformations linked to the directionality of the aminoacylation pathway of nonribosomal peptide synthetases.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are multifunctional megaenzymes that govern the stepwise biosynthesis of pharmaceutically important peptides. In an ATP-dependent assembly-line mechanism dedicated domains are responsible for each catalytic step. Crystal structures have provided insight into several conformations of interacting domains. However, the complete picture in solution of how domain dynamics and the timing of conformational changes effect a directional biosynthesis remains only poorly understood and will be important for the efficient reprogramming of NRPSs. Here we dissect the multiple conformational changes associated with the adenylation and thiolation reactions of the aminoacylation pathway under catalytic conditions. We used pyrophosphate (PP _i ) to b

SUBMITTER: Mayerthaler F 

PROVIDER: S-EPMC8341999 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature