Studies on the cholinesterases inhibiting compounds from the Cassiopea andromeda venom

Cholinesterase inhibitors find application in the combat and care of several diseases, especially AD. Jellyfish venoms are the most promising sources of potent cholinesterase inhibitors. Therefore, it is of interest to study cholinesterases inhibiting compounds from the Cassiopea andromeda venom. We report bioactive compounds using the GC-MC method followed by molecular modeling and docking data analysis. The GC-MS analysis of the crude venom led to the identification of seven bioactive compounds (C1-C7), comprising the steroidal alkaloids, phenolic and carotenoid derivatives. The venom exhibited inhibitory activities against the cholinesterase enzymes. The compound C2, a Dioxolane steroid, displayed the strongest inhibition on both AChE and BChE activities for further consideration.     

Pentapeptide repeat protein QnrB1 requires ATP hydrolysis to rejuvenate poisoned gyrase complexes

DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for a variety of ‘poisons’, namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules (e.g. fluoroquinolones). Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, the mechanism of action of these protective PRPs is not known. We show that a PRP, QnrB1 provides specific protection against fluoroquinolones, which strictly requires ATP hydrolysis by gyrase. QnrB1 binds to the GyrB protein and stimulates ATPase activity of the isolated N-terminal ATPase domain of GyrB (GyrB43). We probed the QnrB1 binding site using site-specific incorporation of a photoreactive amino acid and mapped the crosslinks to the GyrB43 protein. We propose a model in which QnrB1 binding allosterically promotes dissociation of the fluoroquinolone molecule from the cleavage complex.