Drs. Nanette Que and Dan Gewirth at the Hauptman-Woodward Medical Research Institute have published a paper in Proteins: Structure, Function, and Bioinformatics analyzing how drugs bind selectively to a protein that is an emerging therapeutic target for cancer and other diseases.
The report investigates how some drugs selectively target the molecular chaperone protein called Grp94 while avoiding potentially harmful interactions with a close cellular counterpart called Hsp90. Selective inhibition is a key goal of the drug design process, as high selectivity can reduce the side effects of treatment. The group identified just a single alpha helix at the beginning of the protein that was responsible for imparting the selective binding properties. This study answered a long-standing question of how it was possible for some drugs to selectively inhibit just one of two closely related proteins.
The molecular chaperone proteins Grp94 and Hsp90 have been the focus of drug design efforts as part of developing new approaches to cancer treatment. A surprising finding of the paper by Que et al. is that the selective alpha helix identified in Grp94 is also present in the molecular chaperones found in almost every species of fungus. This opens the possibility that drugs previously designed for anti-cancer use may be repurposed for treating deadly fungal infections.
Read the paper by visiting https://doi.org/10.1002/prot.26756.