Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in distinct conformations. The domain organization reveals a unique "H"-shaped head-to-tail dimeric architecture. The capture of both aryl and peptidyl carrier protein-tethered substrates and intermediates inside the heterocyclization domain and L-cysteinyl adenylate in the adenylation domain illustrates the catalytic and recognition residues. The multilevel structural transitions guided by the adenylation C-terminal subdomain in combination with the inserted epimerase and the conformational chang

SUBMITTER: Wang J 

PROVIDER: S-EPMC8807600 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature