BIOL 79 |
| Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) are responsible for the biosynthesis of a wide range of therapeutically important natural products. NRPS and PKS are each composed of independently folded domains, arranged in a linear assembly-line manner. Although structures of multidomain PKS fragments and the related fatty acid synthases have been solved recently, the active conformation of the carrier domains and their attached phosphopantetheinyl arms (derived from coenzyme A) has not been determined. The hydrolytic instability of CoA thioesters at neutral to basic pH severely limits their use as mechanistic probes, especially in structural and biochemical studies. Here we report an approach to manipulate the carrier-domain geometry of NRPS assemblies through the application of isosteric nonhydrolyzable analogues of coenzyme A. Structurally restrained multidomain NRPS assemblies will be useful in elucidating the complex structure and mechanism of synthetases.
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |
