Aztreonam is a Gram-negative bacteria-targeting synthetic monobactam antibiotic. Human serum albumin (HSA) plays an important role in the transference of pharmaceuticals, hormones, and fatty acids, along with other compounds, determining their biodistribution and physiological fate. Using several biophysical and in silico approaches, we studied the interaction of aztreonam with HSA under physiological environments in this study. Results confirm the formation of HSA-aztreonam complex where aztreonam showed moderate affinity towards HSA. A static mode of quenching was confirmed from the steady state fluorescence data. FRET findings also showed that there was a significant feasibility of energy transfer between HSA and aztreonam. Site marker displacement experimental conclusion suggested the binding site of aztreonam was the sub-domain IB of HSA. Circular dichroic spectroscopic analysis suggested that aztreonam interaction decreases the α-helical content of HSA. Changes in microenvironment were studied through synchronous fluorescence data. According to molecular docking results, the HSA-aztreonam complex is mostly maintained by non-covalent forces, with a binding energy of 7.7 kcal mol-1. The presence of a hydrogen bond, van der Waal interaction, and pi-anion interaction in the binding process, as well as conformational changes in HSA after binding with aztreonam, are all confirmed by molecular dynamic simulation.
Keywords: FRET; HSA; aztreonam; docking; simulation.