pyrophosphate and 1-2-oleoylphosphatidylcholine

Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It is synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on phosphatidic acid, a signaling lipid with multifunctional properties. PA functions in the membrane through the interaction of its negatively charged phosphomonoester headgroup with positively charged proteins and ions. DGPP, like PA, can interact electrostatically via the electrostatic-hydrogen bond switch mechanism but differs from PA in its overall charge and shape. The formation of DGPP from PA alters the physicochemical properties as well as the structural dynamics of the membrane. This potentially impacts the molecular and ionic binding of cationic proteins and ions with the DGPP enriched membrane. However, the results of these important interactions in the stress response and in DGPP's overall intracellular function is unknown. Here, using

Topics: Cations, Divalent; Diphosphates; Glycerol; Lysine; Magnetic Resonance Spectroscopy; Models, Molecular; Peptides; Phosphatidylcholines; Proteins; Static Electricity

Mineralization of the skeleton starts within cell-derived matrix vesicles (MVs); then, minerals propagate to the extracellular collagenous matrix. Tissue-nonspecific alkaline phosphatase (TNAP) degrades inorganic pyrophosphate (PP

Topics: 1,2-Dipalmitoylphosphatidylcholine; Adenosine Triphosphate; Alkaline Phosphatase; Animals; Calcification, Physiologic; Cells, Cultured; Cellular Microenvironment; Cholestenones; Cholesterol; Diphosphates; Ergosterol; Liposomes; Male; Minerals; Osteoblasts; Phosphates; Phosphatidylcholines; Rats, Wistar; Surface Properties

The increasing resistance of human pathogens to conventional antibiotics presents a growing threat to the chemotherapeutic management of infectious diseases. The lanthionine antibiotics, still unused as therapeutic agents, have recently attracted significant scientific interest as models for targeting and management of bacterial infections. We investigated the action of one member of this class, subtilin, which permeabilizes lipid membranes in a lipid II-dependent manner and binds bactoprenyl pyrophosphate, akin to nisin. The role the C and N termini play in target recognition was investigated in vivo and in vitro by using the natural N-terminally succinylated subtilin as well as enzymatically truncated subtilin variants. Fluorescence dequenching experiments show that subtilin induces leakage in membranes in a lipid II-dependent manner and that N-succinylated subtilin is roughly 75-fold less active. Solid-state nuclear magnetic resonance was used to show that subtilin forms complexes with membrane isoprenyl pyrophosphates. Activity assays in vivo show that the N terminus of subtilin plays a critical role in its activity. Succinylation of the N terminus resulted in a 20-fold decrease in its activity, whereas deletion of N-terminal Trp abolished activity altogether.

Topics: Alanine; Anti-Bacterial Agents; Bacteriocins; Cell Membrane; Coated Vesicles; Diphosphates; Fluoresceins; Lactococcus lactis; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Peptides; Phosphatidylcholines; Phosphatidylglycerols; Succinic Acid; Sulfides; Tryptophan; Uridine Diphosphate N-Acetylmuramic Acid