ja300007h_si_001.pdf (518.65 kB)
Ring A of Nukacin ISK-1: A Lipid II-Binding Motif for Type-A(II) Lantibiotic
journal contribution
posted on 2012-02-29, 00:00 authored by Mohammad
R. Islam, Mami Nishie, Jun-ichi Nagao, Takeshi Zendo, Sandro Keller, Jiro Nakayama, Daisuke Kohda, Hans-Georg Sahl, Kenji SonomotoRing 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 (KD = 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.