RRC ID 19101
著者 Islam MR, Nishie M, Nagao J, Zendo T, Keller S, Nakayama J, Kohda D, Sahl HG, Sonomoto K.
タイトル Ring A of nukacin ISK-1: a lipid II-binding motif for type-A(II) lantibiotic.
ジャーナル J Am Chem Soc
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.
巻・号 134(8)
ページ 3687-90
公開日 2012-2-29
DOI 10.1021/ja300007h
PMID 22329487
MeSH Anti-Bacterial Agents / chemistry* Anti-Bacterial Agents / pharmacology Bacillus / cytology Bacillus / drug effects Bacteriocins / chemistry* Bacteriocins / pharmacology Binding Sites Cell Wall / chemistry Cell Wall / drug effects Cell Wall / metabolism Lactobacillus / cytology Lactobacillus / drug effects Microbial Sensitivity Tests Staphylococcus / cytology Staphylococcus / drug effects Structure-Activity Relationship Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives* Uridine Diphosphate N-Acetylmuramic Acid / chemistry Uridine Diphosphate N-Acetylmuramic Acid / metabolism
IF 14.612
引用数 43
WOS 分野 CHEMISTRY, MULTIDISCIPLINARY
リソース情報
一般微生物 JCM 1157 JCM 2257 JCM 5803