NMR structure of antibiotics plipastatins A and B from Bacillus subtilis inhibitors of phospholipase A(2).
Plipastatins A and B are antifungal antibiotics belonging to a family of lipopeptides capable of inhibiting phospholipase A(2) (PLA(2)) and are biosynthesised under certain circumstances by Bacillus subtilis. U-(15)N 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 (15)NH(4)Cl. 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 (1)H- and (15)N-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 beta-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 PLA(2).
Volpon
L
L
Laboratoire de RMN Biomoléculaire associé au CNRS, Université Claude Bernard, Lyon 1, Villeurbanne, France.
Besson
F
F
Lancelin
J M
JM
D000595:Amino Acid Sequence; D000643:Ammonium Chloride / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry*; D001412:Bacillus subtilis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004951:Esterification; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009587:Nitrogen Isotopes; D009842:Oligopeptides / Q000096:biosynthesis / Q000737:chemistry*; D010456:Peptides, Cyclic; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D017385:Sequence Homology; D012996:Solutions
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D009587:Nitrogen Isotopes; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012996:Solutions; C049901:plipastatin; D000643:Ammonium Chloride; D010741:Phospholipases A