Inhibition of pathogenic Vibrio harveyi using calamenene, derived from the Indian gorgonian Subergorgia reticulata, and its synthetic analog.

We report the synthesis and antimicrobial properties of a partially reduced dihydronathphthoquinone analogue of 2-methoxy, 5-acetoxy calamenene, extracted from Subergorgia reticulata. The growth of a pathogenic Vibrio harveyi strain was effectively controlled by the calamenene derivative 1 (Cala1) and its synthetic analog 2 (Cala2). Complete mortality of V. harveyi was observed with 2.5 and 0.5 µg mL-1 concentrations of Cala1 and Cala2, respectively. The metabolic assays demonstrated that Cala1 is a bacteriostatic agent while Cala2 showed bactericidal properties. It was confirmed that translocation of Cala2 into the cytoplasm does not induce any change to the integrity of the bacterial cell wall. The Cala2 induced damage to the genetic material of 70% of cells while genetic material of 91% of cells treated with Cala1 remained intact. The Cala2 is, therefore, proposed as a potential bactericidal compound against the aquaculture pathogen V. harveyi. The fact that the Cala2 exhibited minimal cytotoxicity to Artemia nauplii indicates its potential use as an antimicrobial agent for aquaculture operations.

Sequence dependent lipid-mediated effects modulate the dimerization of ErbB2 and its associative mutants.

The association of transmembrane helices is an important event in several biological processes, but the factors governing association, especially the non-specific environmental effects, have still not been elucidated. Here, we use coarse-grain molecular dynamics simulations to study the association of ErbB2 transmembrane helices and three "oncogenic mutants." Self-assembly simulations and the dimerization free-energy profiles confirm an energetically-favorable dimerized state for both the wildtype and the mutants. The dissociation free energy of all three mutants is calculated to be larger than the wildtype peptide. Along with favourable protein-protein interactions, non-specific environmental effects are observed to contribute to the association. In particular, local bilayer thinning along with membrane perturbations are seen around the mutants. The membrane perturbations are reduced upon helix association, suggesting that lipid chain packing is an important driving force for helix dimerization. Our results highlight the importance of both specific as well as non-specific driving forces in the association of transmembrane helices.