LiaRS reporter assay: A simple tool to identify lipid II binding moieties in lantibiotic nukacin ISK-1

Elsayed, Khaled M.; Islam, Mohammad Riazul; Mahin, Abdullah‐Al; Nagao, Jun Ichi; Zendo, Takeshi; Sonomoto, Kenji

doi:10.1016/j.jbiosc.2016.10.002

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…Variants of nukacin ISK-1, lacticin 481, and bovicin HJ50 have been investigated for bioactivity (Figure ). ,− As first shown for mersacidin, the highly conserved Glu/Asp in the ring C lipid II binding motif (A-ring for lacticin/nukacin/bovicin) is essential for bioactivity in all investigated compounds. ,, In addition, Lys residues in these compounds are important for bioactivity, possibly by increasing the affinity for the negatively charged lipids in the bacterial membrane. ,,, Disruption of any of the rings in bovicin HJ50, including the macrocycle generated by disulfide formation, resulted in complete loss of bioactivity . The importance of these rings was also reported for lacticin 481, and synthetic studies showed that the stereochemistry of the three (Me)Lan cross-links is also critical for bioactivity.…”

Section: Lanthipeptides and Compounds Made Via Related Pathwayssupporting

confidence: 69%

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

et al. 2022

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a natural product class that has undergone significant expansion due to the rapid growth in genome sequencing data and recognition that they are made by biosynthetic pathways that share many characteristic features. Their mode of actions cover a wide range of biological processes and include binding to membranes, receptors, enzymes, lipids, RNA, and metals as well as use as cofactors and signaling molecules. This review covers the currently known modes of action (MOA) of RiPPs. In turn, the mechanisms by which these molecules interact with their natural targets provide a rich set of molecular paradigms that can be used for the design or evolution of new or improved activities given the relative ease of engineering RiPPs. In this review, coverage is limited to RiPPs originating from bacteria.

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Section: Lanthipeptides and Compounds Made Via Related Pathwayssupporting

confidence: 69%

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

et al. 2022

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“…Nukacin ISK-1 contains post-translationally modified amino acid residues: lanthionine (Lan), methyllanthionine (MeLan), and dehydrobutyrine (Dhb) (Figure a). The three monosulfide bonds define three lanthionine rings, ring A, ring B, and ring C, which are all essential for the antimicrobial activity. , Our previous NMR structural analysis revealed that nukacin ISK-1 exists as two topological isomers, termed state A [Protein Data Bank (PDB) entry 5Z5Q] and state B (PDB entry 5Z5R). In the main-chain topology, ring C is located above ring A in state A and under ring A in state B (Figure b).…”

mentioning

confidence: 99%

Mosaic Cooperativity in Slow Polypeptide Topological Isomerization Revealed by Residue-Specific NMR Thermodynamic Analysis

Fujinami

Motomura

Oshima

et al. 2020

J. Phys. Chem. Lett.

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Slow polypeptide conformational changes on time scales of >1 s are generally assumed to be highly cooperative two-state transitions, reflecting the high energy barrier. However, few experimental characterizations have tested the validity of this assumption. We performed residue-specific NMR thermodynamic analysis of the 27-residue lantibiotic peptide, nukacin ISK-1, to characterize the isomerization between two topological states on the second time scale. Unexpectedly, the thermal transition behaviors were distinct among peptide regions, indicating that the topological isomerization process is a mosaic of different degrees of cooperativity. The conformational change path between the two NMR structures was deduced by a targeted molecular dynamics simulation. The unique side-chain threading motions through the monosulfide rings are the structural basis of the high energy barrier, and the nonlocal interactions in the hydrophobic core are the structural basis of the cooperativity. Taken together, we provide an energetic description of the topological isomerization of nukacin ISK-1.

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“…Mutations in these areas have been shown to reduce antimicrobial activity. , Halβ and LtnA2 are both Type-A(I)-like lantibiotics with overall charges of +1. The similarities between mersacidin, Halα, and LtnA1 are suggestive of a conserved lipid II binding motif. , …”

Section: Introductionmentioning

confidence: 94%

“… Nisin exerts its antimicrobial effect by pore formation on bacterial membranes, which is enhanced by the presence of lipid II, and binds to lipid II through its N-terminal lanthionine rings, forming a “pyrophosphate cage” . Mersacidin ( 2 ) is a Type-B lantibiotic that also binds to lipid II . 2D-NMR experiments have shown that when lipid II is added to mersacidin, it undergoes several chemical shift perturbations in its C-terminus .…”

Section: Introductionmentioning

confidence: 99%

Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147

et al. 2017

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Lacticin 3147 is a two peptide lantibiotc (LtnA1 and LtnA2) that displays nanomolar activity against many Gram-positive bacteria. Lacticin 3147 may exert its antimicrobial effect by several mechanisms. Isothermal titration calorimetry experiments show that only LtnA1 binds to the peptidoglycan precursor lipid II, which could inhibit peptidoglycan biosynthesis. An experimentally supported model of the resulting complex suggests that the key binding partners are the C-terminus of LtnA1 and pyrophosphate of lipid II. A combination of in vivo and in vitro assays indicates that LtnA1 and LtnA2 can induce rapid membrane lysis without the need for lipid II binding. However, the presence of lipid II substantially increases the activity of lacticin 3147. Furthermore, studies with synthetic LtnA2 analogues containing either desmethyl- or oxa-lanthionine rings confirm that the precise geometry of these rings is essential for this synergistic activity.

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LiaRS reporter assay: A simple tool to identify lipid II binding moieties in lantibiotic nukacin ISK-1

Cited by 9 publications

References 26 publications

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

Mosaic Cooperativity in Slow Polypeptide Topological Isomerization Revealed by Residue-Specific NMR Thermodynamic Analysis

Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147

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