| 9.A.52 The Lasso Peptide Microcin J25 (Microsin J25) Family
Microcin J25 (MccJ25) is a cyclic peptide of 21 unmodified amino acis residues produced by a fecal strain of Escherichia coli. It is mainly directed to Enterobacteriaceae, including several pathogenic E. coli, Salmonella and Shigella strains. Rintoul et al., 2001 showed that MccJ25 acts on the cytoplasmic membrane of Salmonella newport cells producing alterations of the membrane permeability, and subsequent ion gradient dissipation. This initiates the growth inhibition process. This suggest that the disruption of the cytoplasmic memrbane gradient is closely related to the bactericidal activity of MccJ25.The structures of Microcin J25 is known (1S7P_A; 5T56-A-D).
Lasso peptides exist naturally in a threaded state as rotaxanes, and
can be cleaved in their loop regions to serve
as building blocks for catenanes. Mutagenesis of the lasso peptide
microcin J25 (MccJ25) with two cysteine residues followed by cleavage of
the peptide with trypsin led to a [1]rotaxane structure that
self-assembled into a [3]catenane and [4]catenanes
in aqueous solution. The [3]catenane represents the smallest ring size
of a catenane composed solely of polypeptide segments. The NMR structure
of the [3]catenane was determined, suggesting that burial of
hydrophobic residues may be a driving force for assembly of the catenane
structure (Allen and Link 2016).
There are several lasso peptides, all of similar size and general
characteristics. These have not all been shown to affect bacterial
membrane permeability, but many of them are antimicrobial. Although
homology has not been established, some similarity in their primary
amino acid sequences has been noted. These peptides are listed in this
family (Carson et al. 2023).
The reaction probably catalyzed by MccJ25 is:
cations (in) ⇌  cations (out)
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| References: |
Allen, C.D. and A.J. Link. (2016). Self-Assembly of Catenanes from Lasso Peptides. J. Am. Chem. Soc. 138: 14214-14217.
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Braffman, N.R., F.J. Piscotta, J. Hauver, E.A. Campbell, A.J. Link, and S.A. Darst. (2019). Structural mechanism of transcription inhibition by lasso peptides microcin J25 and capistruin. Proc. Natl. Acad. Sci. USA 116: 1273-1278.
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Carson, D.V., M. Patiño, H.E. Elashal, A.J. Cartagena, Y. Zhang, M.E. Whitley, L. So, A.K. Kayser-Browne, A.M. Earl, R.P. Bhattacharyya, and A.J. Link. (2023). Cloacaenodin, an Antimicrobial Lasso Peptide with Activity against. ACS Infect Dis 9: 111-121.
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Mukhopadhyay, J., E. Sineva, J. Knight, R.M. Levy, and R.H. Ebright. (2004). Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol. Cell 14: 739-751.
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Rintoul, M.R., B.F. de Arcuri, R.A. Salomón, R.N. Farías, and R.D. Morero. (2001). The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport. FEMS Microbiol. Lett. 204: 265-270.
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Socias, S.B., K. Severinov, and R.A. Salomon. (2009). The Ile13 residue of microcin J25 is essential for recognition by the receptor FhuA, but not by the inner membrane transporter SbmA. FEMS Microbiol. Lett. 301: 124-129.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 9.A.52.1.1 | Microcin J25 (MccJ25) cyclic 21 aa peptide, derived from a precursor of 58 aas. The Ile13 residue of microcin J25 is essential for recognition by the receptor FhuA, but not by the inner membrane transporter SbmA (Socias et al., 2009). It inhibits transcription by binding deep within RNAP
secondary channel, where it sterically blocks the folding of the
trigger loop, which is essential for efficient catalysis (Mukhopadhyay et al. 2004; Braffman et al. 2019). It also acts on the cytoplasmic membrane of
Salmonella newport, producing alteration of membrane permeability and
subsequent gradient dissipation, which inhibits
several processes essential for cell viability, such as oxygen
consumption (Rintoul et al. 2001). | Bacteria | Microcin J25 of E. coli (Q9X2V7) |
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| 9.A.52.1.2 | Citrocin of 19 aas | | Citrocin of Citrobacter pasteurii |
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| 9.A.52.1.3 | Cloacaenodin of 24 aas | | Cloacaenodin of Enterobacter hormaechei |
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| 9.A.52.1.4 | Klebsidin of 19 aas (similar in sequence to other lasso peptides), but derived from a protein of 45 aas, Pre-klebsidin, listed here. | | Klebsidin of Klebsiella pneumoniae |
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| 9.A.52.1.5 | Capistruin of 19 aas, but derived from a larger pepdide as are all of the lasso peptides that exhibit anti-microbial activity. | | Capistruin of Burkholderia |
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| 9.A.52.1.6 | Pre-capistruin of 47 aas. This precursor is processed to capistruin (TC# 9.A.52.1.5) | | Pre-capistruin of Burkholderia |
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