mGBP8 Activators

The initial discovery of such activators would likely begin with the development of a biochemical assay designed to measure the GTPase activity of mGBP8. This assay could be based on the protein's ability to hydrolyze GTP to GDP, a reaction that can be monitored using various techniques, such as the release of inorganic phosphate or the use of fluorescently labeled GTP analogs. The high-throughput screening (HTS) of chemical libraries using these assays would aim to identify compounds that increase the GTP hydrolysis rate, signifying enhanced mGBP8 activity. Hits from the HTS would be considered candidate mGBP8 activators and would be subjected to further validation to confirm their specific activity.

Once candidate activators are identified, secondary validation involves a more detailed examination of the interaction between these molecules and mGBP8. Techniques such as isothermal titration calorimetry (ITC) would provide data on the thermodynamics of the binding interaction, while surface plasmon resonance (SPR) would offer insight into the kinetics of the activator binding to mGBP8. These methods would help confirm whether the observed increase in activity is due to a direct effect of the activator on mGBP8. Further studies, including X-ray crystallography or cryo-electron microscopy (cryo-EM), could provide a detailed three-dimensional structure of the mGBP8 in complex with the activator, shedding light on the molecular basis for activation.