NMR structure of antibiotics plipastatins A and B from Bacillus subtilis inhibitors of phospholipase A2

FEBS Letters

Lancelin, Jean-Marc²  Besson, Françoise¹  Volpon, Laurent² 

[1] Laboratoire de Physico-Chimie Biologique associé au CNRS, Université Claude Bernard, Lyon 1, Bâtiment 303, F-69622 Villeurbanne, France;Laboratoire de RMN Biomoléculaire associé au CNRS, Université Claude Bernard, Lyon 1 and Ecole Supérieure de Chimie Physique et Electronique de Lyon, Bâtiment 308G, F-69622 Villeurbanne, France

关键词: Antifungal antibiotic;    Plipastatin;    Nuclear magnetic resonance spectroscopy;    Phospholipase A2 inhibitor;    Solution structure;    Bacillus subtilis;    DMSO;    dimethylsulfoxide;    HSQC;    heteronuclear single quantum coherence;    PLA2;    phospholipase A2;    SA;    simulated annealing;    rmsd;    root mean square deviation;   

DOI  :  10.1016/S0014-5793(00)02182-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Plipastatins A and B are antifungal antibiotics belonging to a family of lipopeptides capable of inhibiting phospholipase A₂ (PLA₂) and are biosynthesised under certain circumstances by Bacillus subtilis. U-¹⁵N plipastatins A and B were obtained from cultures of the strain NCIB 8872 on a Landy medium modified for stable-isotope labelling by the substitution of the L-glutamic acid used as the sole nitrogen source, by ¹⁵NH₄Cl. These two lipo-decapeptides, lactonised by esterification of the Ile10 C-terminus with the phenolic hydroxyl of Tyr3, differ only by a D-Ala (plipastatin A)/D-Val (plipastatin B) substitution at the position 6. The ¹H- and ¹⁵N-nuclear magnetic resonance (NMR) signals of a 4:6 mixture of plipastatins A and B were unambiguously assigned and their structures in dimethylsulfoxide solution were calculated on the basis of a set of NMR-derived restraints. Plipastatins A and B are well-defined structures in solution stabilised by a type 1 β-turn comprising residues 6–9 and several other specific hydrogen bonds. The structures afford a first molecular basis for the future studies of their biological activities both in lipidic layers or on PLA₂.

【 授权许可】

Unknown