6om4
From Proteopedia
The structure of Microcin C7 biosynthetic enzyme MccB in complex with N-formylated MccA
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 PubMedMicrocin 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
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