Functional and mechanistic analyses of biomimetic aminoacyl transfer reactions in de novo designed coiled coil peptides via rational active site engineering.

ABSTRACT: Ribosomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a series of directed intermodular aminoacyl transfer reactions. We recently reported the design of coiled-coil assemblies that could functionally mimic the elementary aminoacyl loading and intermodular aminoacyl transfer steps of NRPSs. These peptides were designed initially to accelerate aminoacyl transfer mainly through catalysis by approximation by closely juxtaposing four active site moieties, two each from adjacent noncovalently associated helical modules. In our designs peptide self-assembly positions a cysteine residue that is used to covalently capture substrates from solution via transthiolesterification (substrate loading step to generate the aminoacyl donor site) adjacent to an

SUBMITTER: Leman LJ 

PROVIDER: S-EPMC2453064 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature