Multiple substrate recognition by yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase through phosphate clamping

• DOI: 10.1126/sciadv.abf6744
• Publication Date: 2021-04-23T19:47:14Z
• Authors: María Ángeles Már...; Raquel Ortega-García; Megan L. Shipton; Elsa Franco-Echev...; Andrew M. Riley; Julia Sanz-Aparicio; Barry V. L. Potter; Beatriz González
• Keywords: Polyphosphate; Inorganic pyrophosphatase; Pyrophosphatases

The yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase DDP1 is a Nudix enzyme with pyrophosphatase activity on diphosphoinositides, dinucleotides, polyphosphates. These substrates bind to diverse protein targets participate in signaling metabolism, being essential for energy phosphate homeostasis, ATPase pump regulation, or phosphorylation. An exhaustive structural study of complex multiple ligands related its three substrate classes reported. This allowed full characterization the active site depicting molecular basis endowing multisubstrate abilities enzyme, driven by anchoring following defined path. study, combined variants, reveals different binding modes, preferences, selection. Our findings expand current knowledge this important superfamily implications extending beyond inositide research. work represents valuable tool inhibitor/substrate design ScDDP1 orthologs as potential address fungal infections other health concerns.