BIOL 94 |
| Fatty acid, polyketide, and nonribosomal peptide synthases are multimodular megaproteins that utilize the carrier protein to mediate the biosynthesis of secondary metabolites. The carrier protein functions as a scaffold, tethering the building blocks as the constituent elements are assembled and modified by the different domains in the megasynthase. Recently, we reported the development of mechanism-based protein cross-linking probes that selectively cross-linked type II fatty acid and polyketide acyl carrier proteins with the ketosynthase domains of type II fatty acid synthases in Escherichia coli. These probes were designed to covalently modify the ACPs via post-translational modification with mechanism-based inhibitor moieties. The inhibitors were composed of epoxide or chloroacrylate moieties that were designed to trap the active site cysteine residue of ketosynthase domains. Based on these mechanism-based cross-linking reagents, a panel of compounds was produced to investigate the protein-protein interactions and proximity effects of carrier protein-mediated acyl transfer systems. |
|
Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |