| Structural highlights
Function
[MCCC7_ECOLX] Antibacterial peptide, active against enterobacteria including species of Klebsiella, Salmonella, Shigella, Yersinia and Proteus, and strains of E.coli. Inhibits protein translation by blocking aspartyl-tRNA synthetase function and inhibiting production of aminoacetylated tRNA-Asp.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Microcin C7 (McC) is a peptide antibiotic modified by a linkage of the terminal isoAsn amide to AMP via a phosphoramidate bond. Post-translational modification on this ribosomally produced heptapeptide precursor is carried out by MccB, which consumes two equivalents of ATP to generate the N-P linkage. We demonstrate that MccB only efficiently processes the precursor heptapeptide that retains the N-formylated initiator Met (fMet). Binding studies and kinetic measurements evidence the role of the N-formyl moiety. Structural data show that the N-formyl peptide binding results in an ordering of residues in the MccB "crossover loop", which dictates specificity in homologous ubiquitin activating enzymes. The N-formyl peptide exhibits substrate inhibition, and cannot be displaced from MccB by the desformyl counterpart. Such substrate inhibition may be a strategy to avert unwanted McC buildup and avert toxicity in the cytoplasm of producing organisms.
Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor.,Dong SH, Kulikovsky A, Zukher I, Estrada P, Dubiley S, Severinov K, Nair SK Chem Sci. 2018 Dec 26;10(8):2391-2395. doi: 10.1039/c8sc03173h. eCollection 2019 , Feb 28. PMID:30881667[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garcia-Bustos JF, Pezzi N, Mendez E. Structure and mode of action of microcin 7, an antibacterial peptide produced by Escherichia coli. Antimicrob Agents Chemother. 1985 May;27(5):791-7. PMID:2861788
- ↑ Metlitskaya A, Kazakov T, Kommer A, Pavlova O, Praetorius-Ibba M, Ibba M, Krasheninnikov I, Kolb V, Khmel I, Severinov K. Aspartyl-tRNA synthetase is the target of peptide nucleotide antibiotic Microcin C. J Biol Chem. 2006 Jun 30;281(26):18033-42. Epub 2006 Mar 30. PMID:16574659 doi:10.1074/jbc.M513174200
- ↑ Kazakov T, Vondenhoff GH, Datsenko KA, Novikova M, Metlitskaya A, Wanner BL, Severinov K. Escherichia coli peptidase A, B, or N can process translation inhibitor microcin C. J Bacteriol. 2008 Apr;190(7):2607-10. doi: 10.1128/JB.01956-07. Epub 2008 Jan 25. PMID:18223070 doi:10.1128/JB.01956-07
- ↑ Guijarro JI, Gonzalez-Pastor JE, Baleux F, San Millan JL, Castilla MA, Rico M, Moreno F, Delepierre M. Chemical structure and translation inhibition studies of the antibiotic microcin C7. J Biol Chem. 1995 Oct 6;270(40):23520-32. PMID:7559516
- ↑ Duquesne S, Petit V, Peduzzi J, Rebuffat S. Structural and functional diversity of microcins, gene-encoded antibacterial peptides from enterobacteria. J Mol Microbiol Biotechnol. 2007;13(4):200-9. PMID:17827970 doi:10.1159/000104748
- ↑ Severinov K, Semenova E, Kazakov A, Kazakov T, Gelfand MS. Low-molecular-weight post-translationally modified microcins. Mol Microbiol. 2007 Sep;65(6):1380-94. Epub 2007 Aug 17. PMID:17711420 doi:10.1111/j.1365-2958.2007.05874.x
- ↑ Dong SH, Kulikovsky A, Zukher I, Estrada P, Dubiley S, Severinov K, Nair SK. Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor. Chem Sci. 2018 Dec 26;10(8):2391-2395. doi: 10.1039/c8sc03173h. eCollection 2019 , Feb 28. PMID:30881667 doi:http://dx.doi.org/10.1039/c8sc03173h
|
