Ring A of nukacin ISK-1

A lipid II-binding motif for type-A(II) lantibiotic

Mohammad R. Islam, Mami Nishie, Jun Ichi Nagao, Takeshi Zendo, Sandro Keller, Jiro Nakayama, Daisuke Kohda, Hans Georg Sahl, Kenji Sonomoto

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Ring A of nukacin ISK-1, which is also present in different type-A(II) lantibiotics, resembles a lipid II-binding motif (TxS/TxD/EC, x denotes undefined residues) similar to that present in mersacidin (type-B lantibiotics), which suggests that nukacin ISK-1 binds to lipid II as a docking molecule. Results from our experiments on peptidoglycan precursor (UDP-MurNAc-pp) accumulation and peptide antagonism assays clearly indicated that nukacin ISK-1 inhibits cell-wall biosynthesis, accumulating lipid II precursor inside the cell, and the peptide activity can be repressed by lipid I and lipid II. Interaction analysis of nukacin ISK-1 and different ring A variants with lipid II revealed that nukacin ISK-1 and nukacin D13E (a more active variant) have a high affinity (K D = 0.17 and 0.19 μM, respectively) for lipid II, whereas nukacin D13A (a less active variant) showed a lower affinity, and nukacin C14S (a negative variant lacking the ring A structure) exhibited no interaction. Therefore, on the basis of the structural similarity and positional significance of the amino acids in this region, we concluded that nukacin ISK-1 binds lipid II via its ring A region and may lead to the inhibition of cell-wall biosynthesis.

    Original languageEnglish
    Pages (from-to)3687-3690
    Number of pages4
    JournalJournal of the American Chemical Society
    Volume134
    Issue number8
    DOIs
    Publication statusPublished - Feb 29 2012

    Fingerprint

    Bacteriocins
    Lipids
    Biosynthesis
    Cell Wall
    Peptides
    Uridine Diphosphate
    Peptidoglycan
    nukacin ISK-1
    muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
    Assays
    Amino acids
    Cells
    Amino Acids
    Molecules

    All Science Journal Classification (ASJC) codes

    • Catalysis
    • Chemistry(all)
    • Biochemistry
    • Colloid and Surface Chemistry

    Cite this

    Ring A of nukacin ISK-1 : A lipid II-binding motif for type-A(II) lantibiotic. / Islam, Mohammad R.; Nishie, Mami; Nagao, Jun Ichi; Zendo, Takeshi; Keller, Sandro; Nakayama, Jiro; Kohda, Daisuke; Sahl, Hans Georg; Sonomoto, Kenji.

    In: Journal of the American Chemical Society, Vol. 134, No. 8, 29.02.2012, p. 3687-3690.

    Research output: Contribution to journalArticle

    Islam, Mohammad R. ; Nishie, Mami ; Nagao, Jun Ichi ; Zendo, Takeshi ; Keller, Sandro ; Nakayama, Jiro ; Kohda, Daisuke ; Sahl, Hans Georg ; Sonomoto, Kenji. / Ring A of nukacin ISK-1 : A lipid II-binding motif for type-A(II) lantibiotic. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 8. pp. 3687-3690.
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    abstract = "Ring A of nukacin ISK-1, which is also present in different type-A(II) lantibiotics, resembles a lipid II-binding motif (TxS/TxD/EC, x denotes undefined residues) similar to that present in mersacidin (type-B lantibiotics), which suggests that nukacin ISK-1 binds to lipid II as a docking molecule. Results from our experiments on peptidoglycan precursor (UDP-MurNAc-pp) accumulation and peptide antagonism assays clearly indicated that nukacin ISK-1 inhibits cell-wall biosynthesis, accumulating lipid II precursor inside the cell, and the peptide activity can be repressed by lipid I and lipid II. Interaction analysis of nukacin ISK-1 and different ring A variants with lipid II revealed that nukacin ISK-1 and nukacin D13E (a more active variant) have a high affinity (K D = 0.17 and 0.19 μM, respectively) for lipid II, whereas nukacin D13A (a less active variant) showed a lower affinity, and nukacin C14S (a negative variant lacking the ring A structure) exhibited no interaction. Therefore, on the basis of the structural similarity and positional significance of the amino acids in this region, we concluded that nukacin ISK-1 binds lipid II via its ring A region and may lead to the inhibition of cell-wall biosynthesis.",
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    AU - Nagao, Jun Ichi

    AU - Zendo, Takeshi

    AU - Keller, Sandro

    AU - Nakayama, Jiro

    AU - Kohda, Daisuke

    AU - Sahl, Hans Georg

    AU - Sonomoto, Kenji

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