C60 fullerenes are spherical molecules com posed purely of carbon atoms. They inspire a particularly strong scientific interest because of their specific physico chemical properties and potential medical and nanotech nological applications. In this work we are focusing on studying the influence of the pristine C60 fullerene on bio logical activity of some aromatic drug molecules in human buccal epithelial cells. Assessment of the heterochromatin structure in the cell nucleus as well as the barrier function of the cell membrane was performed. The methods of cell microelectrophoresis and atomic force microscopy were also applied. A concentration-dependent restoration of the functional activity of the cellular nucleus after exposure to DNA-binding drugs (doxorubicin, proflavine and ethidium bromide) has been observed in human buccal epithelial cells upon addition of C60 fullerene at a concentration of -1СГ5 M. The results were shown to follow the framework of interceptor/protector action theory, assuming that noncovalent complexation between C60 fullerene and the drugs (i.e., hetero-association) is the major process responsible for the observed biological effects. An independent con firmation of this hypothesis was obtained via investigation of the cellular response of buccal epithelium to the coad ministration of the aromatic drugs and caffeine, and it is based on the well-established role of hetero-association in drug-caffeine systems. The results indicate that C60 fuller ene may reverse the effects caused by the aromatic drugs, thereby pointing out the potential possibility of the use of aromatic drugs in combination with C60 fullerene for regu lation of their medico-biological action.
Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. For K. pneumoniae, this is the first high-resolution cleavage complex structure to be reported.
Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme–DNA interface for drug discovery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.