Specific disulfide cross-linking to constrict the mobile carrier domain of nonribosomal peptide synthetases.

ABSTRACT: Nonribosomal peptide synthetases are large, multi-domain enzymes that produce peptide molecules with important biological activity such as antibiotic, antiviral, anti-tumor, siderophore and immunosuppressant action. The adenylation (A) domain catalyzes two reactions in the biosynthetic pathway. In the first reaction, it activates the substrate amino acid by adenylation and in the second reaction it transfers the amino acid onto the phosphopantetheine arm of the adjacent peptide carrier protein (PCP) domain. The conformation of the A domain differs significantly depending on which of these two reactions it is catalyzing. Recently, several structures of A-PCP di-domains have been solved using mechanism-based inhibitors to trap the PCP domain in the A domain active site. Here, we present an a

SUBMITTER: Tarry MJ 

PROVIDER: S-EPMC4502403 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature