Targeting Phosphoglycerate Kinases by Tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, by a proteomic platform

Tatridin A (TatA) is a germacrane sesquiterpenoid that contains one E- and one Z- double bond in its 10-membered ring, which is fused to a 3-methylene-di-hydrofuran-2-one moiety. Through a combination of limited proteolysis and molecular docking, it has been discovered that TatA interacts with the active domains of Phosphoglycerate Kinase 1 (PGK1), thereby altering its hinge region. This interaction may account for TatA's inhibitory potency on the enzyme activity. The pdb files of the best complex between TatA and human PGK1 (pdbID: 2WZB) and human PGK2 (obtained from the AlphaFold database with identification number AF-P07205-F1) are reported here, obtained through molecular docking analysis performed using the SwissDock web server.