3R9G: Crystal structure of Microcin C7 self immunity acetyltransferase MccE in complex with Coenzyme A and processed Microcin C7 antibiotic

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 shown previously 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 studies of the MccE acetyltransferase domain (MccE(AcTase)). 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 MccE(AcTase) can detoxify a range of aminoacylnucleotides, including those that are structurally distinct from microcin C7.
PDB ID: 3R9GDownload
MMDB ID: 90218
PDB Deposition Date: 2011/3/25
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.35  Å
Source Organism:
Similar Structures:
Biological Unit for 3R9G: monomeric; determined by author and by software (PISA)
Molecular Components in 3R9G
Label Count Molecule
Protein (1 molecule)
Mcce Protein
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB