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 li popeptides capable of inhibiting phospholipase A(2) (PLA(2)) and are biosyn thesised under certain circumstances by Bacillus subtilis. U-N-15 plipastat ins 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-g lutamic acid used as the sole nitrogen source, by (NH4Cl)-N-15. These two l ipo-decapeptides, lactonised by esterification of the Ile10 C-terminus with the phenolic hydroxyl of Tyr3, differ only by a D-Ala (plipastatin A)/D-Va l (plipastatin B) substitution at the position 6. The H-1- and N-15-nuclear magnetic resonance (NMR) signals of a 4:6 mixture of plipastatins A and B were unambiguously assigned and their structures in dimethylsulfoxide solut ion were calculated on the basis of a set of NMR-derived restraints. Plipas tatins 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 b onds. The structures afford a first molecular basis for the future studies of their biological activities both in lipidic layers or on PLA2. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.