PMID:22516613

Citation	Nocek, B, Tikhonov, A, Babnigg, G, Gu, M, Zhou, M, Makarova, KS, Vondenhoff, G, Van Aerschot, A, Kwon, K, Anderson, WF, Severinov, K and Joachimiak, A (2012) Structural and functional characterization of microcin C resistance peptidase MccF from Bacillus anthracis. J. Mol. Biol. 420:366-83
Abstract	Microcin C (McC) is heptapeptide adenylate antibiotic produced by Escherichia coli strains carrying the mccABCDEF gene cluster encoding enzymes, in addition to the heptapeptide structural gene mccA, necessary for McC biosynthesis and self-immunity of the producing cell. The heptapeptide facilitates McC transport into susceptible cells, where it is processed releasing a non-hydrolyzable aminoacyl adenylate that inhibits an essential aminoacyl-tRNA synthetase. The self-immunity gene mccF encodes a specialized serine peptidase that cleaves an amide bond connecting the peptidyl or aminoacyl moieties of, respectively, intact and processed McC with the nucleotidyl moiety. Most mccF orthologs from organisms other than E. coli are not linked to the McC biosynthesis gene cluster. Here, we show that a protein product of one such gene, MccF from Bacillus anthracis (BaMccF), is able to cleave intact and processed McC, and we present a series of structures of this protein. Structural analysis of apo-BaMccF and its adenosine monophosphate complex reveals specific features of MccF-like peptidases that allow them to interact with substrates containing nucleotidyl moieties. Sequence analyses and phylogenetic reconstructions suggest that several distinct subfamilies form the MccF clade of the large S66 family of bacterial serine peptidases. We show that various representatives of the MccF clade can specifically detoxify non-hydrolyzable aminoacyl adenylates differing in their aminoacyl moieties. We hypothesize that bacterial mccF genes serve as a source of bacterial antibiotic resistance.
Links	PubMed PMC3690760 Online version:10.1016/j.jmb.2012.04.011
Keywords	Adenosine Monophosphate/metabolism; Amino Acid Sequence; Amino Acyl-tRNA Synthetases/metabolism; Anti-Bacterial Agents/pharmacology; Bacillus anthracis/enzymology; Bacillus anthracis/genetics; Bacteriocins/pharmacology; Crystallography, X-Ray; Drug Resistance, Bacterial/genetics; Genes, Bacterial; Models, Chemical; Molecular Sequence Data; Peptide Hydrolases/chemistry; Peptide Hydrolases/genetics; Peptide Hydrolases/metabolism; Phylogeny; Protein Conformation; Sequence Homology, Amino Acid; Serine Endopeptidases/chemistry; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism; Substrate Specificity
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECOLX:MCCF		GO:0008236: serine-type peptidase activity	ECO:0000315:		F		Figure 2: Based on this result we conclude that similarly to EcMccF, BaMccF likely cleaves the C-N bond in the carboxamide moiety of in DSA and ESA. Inactivations of McC by BaMccF likely occurs by the same mechanism. We therefore conclude that the MccF proteins from E. coli and B. anthracis are functionally equivalent to one another.	complete CACAO 10015

References

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