3r96

Publication Abstract from PubMed

The antibiotic microcin C7 (McC) acts as a bacteriocide by inhibiting aspartyl tRNA synthetase, and stalling the protein translation machinery. McC is synthesized as a heptapeptide-nucleotide conjugate, which is processed by cellular peptidases within target strains to yield the biologically active compound. As unwanted processing of intact McC can result in self-toxicity, producing strains utilize multiple mechanisms for autoimmunity against processed McC. We have previously shown that the mccE gene within the biosynthetic cluster can inactivate processed McC by acetylating the antibiotic. Here, we present the characterization of this acetylation mechanism through biochemical and structural biological characterization of the acetyltransferase domain of MccE (MccEAcTase). We have also determined five crystal structures of the MccE-acetyl CoA complex with bound substrates, inhibitor and reaction product. The structural data reveal an unexpected mode of substrate recognition through pi-stacking interactions, similar to those found in cap binding proteins and nucleotidyltransferases. These studies provide a rationale for the observation that MccEAcTase can detoxify a range of aminoacyl-nucleotides, including those that are structurally distinct from microcin C7.

Structural basis for Microcin C7 inactivation by the MccE acetyltransferase.,Agarwal V, Metlytskaya A, Severinov KV, Nair SK J Biol Chem. 2011 Apr 19. PMID:21507941^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.