| Structural highlights
Function
MCJA_ECOLX Peptide antibiotic that functions through inhibition of the bacterial DNA-dependent RNA polymerase (RNAP). May inhibit transcription by binding in RNAP secondary channel and blocking nucleotide substrates access to the catalytic center. Exhibits potent bacteriocidal activity against a range of Enterobacteriaceae, including several pathogenic E.coli, Salmonella and Shigella strains. Also acts on the cytoplasmic membrane of Salmonella newport, producing alteration of membrane permeability and disruption of the subsequent gradient dissipation, which inhibits several processes essential for cell viability, such as oxygen consumption. Induces bacterial filamentation in susceptible cells in a non-SOS-dependent way, but this phenotype may result from impaired transcription of genes coding for cell division proteins.[1] [2] [3]
Publication Abstract from PubMed
Microcin J25 is a 21 amino acid bacterial peptide that has potent antibacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The peptide was previously proposed to have a head-to-tail cyclized peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747-755). It exhibits remarkable thermal stability for a peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is prevented by two aromatic residues flanking the embedded ring. Unthreading does not occur even when the molecule is enzymatically digested with thermolysin. The new structural interpretation fully accounts for previously reported NMR and biophysical data and is consistent with the remarkable stability of this potent antimicrobial peptide.
Microcin J25 has a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone.,Rosengren KJ, Clark RJ, Daly NL, Goransson U, Jones A, Craik DJ J Am Chem Soc. 2003 Oct 15;125(41):12464-74. PMID:14531690[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rintoul MR, de Arcuri BF, Salomon RA, Farias RN, Morero RD. The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport. FEMS Microbiol Lett. 2001 Nov 13;204(2):265-70. PMID:11731133
- ↑ Delgado MA, Rintoul MR, Farias RN, Salomon RA. Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25. J Bacteriol. 2001 Aug;183(15):4543-50. PMID:11443089 doi:http://dx.doi.org/10.1128/JB.183.15.4543-4550.2001
- ↑ Yuzenkova J, Delgado M, Nechaev S, Savalia D, Epshtein V, Artsimovitch I, Mooney RA, Landick R, Farias RN, Salomon R, Severinov K. Mutations of bacterial RNA polymerase leading to resistance to microcin j25. J Biol Chem. 2002 Dec 27;277(52):50867-75. Epub 2002 Oct 24. PMID:12401787 doi:http://dx.doi.org/10.1074/jbc.M209425200
- ↑ Rosengren KJ, Clark RJ, Daly NL, Goransson U, Jones A, Craik DJ. Microcin J25 has a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone. J Am Chem Soc. 2003 Oct 15;125(41):12464-74. PMID:14531690 doi:10.1021/ja0367703
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