title: Ring A of nukacin ISK-1: a lipid II-binding motif for type-A(II) lantibiotic.
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.
authors.affiliation: Laboratory of Microbial Technology, Department of Bioscience and Biotechnology, Faculty of Agriculture, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Islam
authors.forename: Mami
authors.initials: M
authors.lastname: Nishie
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nagao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Zendo
authors.forename: Sandro
authors.initials: S
authors.lastname: Keller
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohda
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001407:Bacillus / Q000166:cytology / Q000187:drug effects; D001430:Bacteriocins / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007778:Lactobacillus / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013210:Staphylococcus / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C421186:nukacin ISK-1