2MH5

Structure and NMR assignments of lantibiotic NAI-107 in DPC micelles

2MH5 の概要

• エントリーDOI: 10.2210/pdb2mh5/pdb
• NMR情報: BMRB: 19619
• 関連するBIRD辞書のPRD_ID: PRD_001219
• 分子名称: Lantibiotic 107891, dodecyl 2-(trimethylammonio)ethyl phosphate (2 entities in total)
• 機能のキーワード: lantibiotic, antibiotic
• 由来する生物種: Microbispora
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25088.06

構造登録者

Munch, D.,Muller, A.,Schneider, T.,Kohl, B.,Wenzel, M.,Bandow, J.,Maffioli, S.,Sosio, M.,Donadio, S.,Wimmer, R.,Sahl, H. (登録日: 2013-11-18, 公開日: 2014-03-05, 最終更新日: 2024-07-10)

主引用文献

Munch, D.,Muller, A.,Schneider, T.,Kohl, B.,Wenzel, M.,Bandow, J.E.,Maffioli, S.,Sosio, M.,Donadio, S.,Wimmer, R.,Sahl, H.G.
The Lantibiotic NAI-107 Binds to Bactoprenol-bound Cell Wall Precursors and Impairs Membrane Functions.
J.Biol.Chem., 289:12063-12076, 2014

PubMed Abstract: The lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance (NMR). The lantibiotic efficiently interfered with late stages of cell wall biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N-acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Using membrane preparations and a complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes (MraY, MurG, FemX, PBP2) and their respective purified substrates, we showed that NAI-107 forms complexes with bactoprenol-pyrophosphate-coupled precursors of the bacterial cell wall. Titration experiments indicate that first a 1:1 stoichiometric complex occurs, which then transforms into a 2:1 (peptide: lipid II) complex, when excess peptide is added. Furthermore, lipid II and related molecules obviously could not serve as anchor molecules for the formation of defined and stable nisin-like pores, however, slow membrane depolarization was observed after NAI-107 treatment, which could contribute to killing of the bacterial cell.

PubMed: 24627484
DOI: 10.1074/jbc.M113.537449

実験手法

SOLUTION NMR