Computational Insights into Amide Bond Formation Catalyzed by the Condensation Domain of Nonribosomal Peptide Synthetases.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are important enzymes that synthesize an array of nongenetically encoded peptides. The latter have diverse physicochemical properties and roles. NRPSs are modular enzymes in which, for example, the condensation (C-) domain catalyzes the formation of amide bonds. The NRPS tyrocidine synthetase from Brevibacillus brevis is responsible for synthesizing the cyclic-peptide antibiotic tyrocidine. The first step is formation of an amide bond between a proline and phenylalanine which is catalyzed by a C-domain. In this study, a multiscale computational approach (molecular dynamics and QM/MM) has been used to investigate substrate binding and catalytic mechanism of the C-domain of tyrocidine synthetase. Overall, the mechanism is found to proceed throu

SUBMITTER: Mansour B 

PROVIDER: S-EPMC11223147 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature