Mycalolide-B, a novel and specific inhibitor of actomyosin ATPase isolated from marine sponge

AbstractA toxin isolated from marine sponge, mycalolide-B, inhibited smooth muscle contractions without changing cytosolic Ca2+ levels. It also inhibited Ca2+-induced contraction in permeabilized smooth muscles. In native actomyosin prepared from chicken gizzard, mycalolide-B inhibited superprecipitation and Mg2+-ATPase activity stimulated by Ca2+ without changing myosin light chain phosphorylation. In the permeabilized muscle and native actomyosin preparation thiophosphorylated with ATPγS, mycalolide-B inhibited ATP-induced contraction and Mg2+-ATPase activity, respectively, in the absence of Ca2+. Mycalolide-B also inhibited Mg2+-ATPase activity of skeletal muscle native actomyosin. Mycalolide-B had no effect on calmodulin-stimulated (Ca2+Mg2+)-ATPase activity of erythrocyte membranes. These results suggest that mycalolide-B selectively inhibits actin—myosin interaction

Crystal Structure of the Complex between Calyculin A and the Catalytic Subunit of Protein Phosphatase 1

AbstractThe crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1γ, in complex with a marine toxin, calyculin A, was determined at 2.0 Å resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseudocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1γ, which is consistent with findings from the studies of dose-inhibition analysis

Biotechnological potential of marine natural products

The number of marine natural products (MNPs) that have been applied to biotechnological industry is very limited, although nearly 20000 new compounds were discovered from marine organisms since the birth of MNPs in the early 1970s. However, it is apparent that they have a significant potential as pharmaceuticals, cosmetics, nutraceuticals, research tools, and others. This article focuses on selective antitumor metabolites isolated from marine sponges and tunicates, and their modes of action, as well as promising candidates for nontoxic antifoulants discovered from marine organisms

Behavioral assay and chemical characters of female sex pheromones in the hermit crab Pagurus filholi

Males of the hermit crab Pagurus filholi perform assessment behavior toward females, as a preliminary step of precopulatory guarding, during the reproductive season. It is known that such behavior is elicited by female sex pheromones, but the compounds involved have never been characterized in this species. Several experiments were conducted to develop a reliable bioassay along with purification procedures to identify potential compounds with pheromonal activity in Pagurus filholi. We developed a bioassay protocol to assess pheromonal activity by using an empty shell with cotton containing either artificial seawater (control) or test water. We measured and compared the time duration of male assessment behavior toward each shell if the test water contained female sex pheromones. Ultra-filtering of seawater samples potentially containing pheromones showed that the compound was < 1 kDa in molecular weight. Males showed precopulatory assessment behavior toward "female conditioned" water samples treated with open column purification and eluted with MeOH, suggesting that compounds triggering male behavior were low polar molecules. Molecules with pheromonal activity were not volatile after freeze drying, effective even after heating to 90 A degrees C, and remained active in seawater at 12 A degrees C even after 6 days from sample collection, which suggests a rather stable characteristic of the female sex pheromones of this species