7AUK
Yeast Diphosphoinositol Polyphosphate Phosphohydrolase DDP1 in complex with 5-InsP7
Summary for 7AUK
| Entry DOI | 10.2210/pdb7auk/pdb |
| Related | 7AUI 7AUJ |
| Descriptor | Diphosphoinositol polyphosphate phosphohydrolase DDP1, (1r,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl trihydrogen diphosphate (3 entities in total) |
| Functional Keywords | inositol, pp-insp, pyrophosphatase, polyphosphate, diadenosine polyphosphate, ddp1, nudix, hydrolase |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 22552.73 |
| Authors | Marquez-Monino, M.A.,Gonzalez, B. (deposition date: 2020-11-03, release date: 2021-05-19, Last modification date: 2024-01-31) |
| Primary citation | Marquez-Monino, M.A.,Ortega-Garcia, R.,Shipton, M.L.,Franco-Echevarria, E.,Riley, A.M.,Sanz-Aparicio, J.,Potter, B.V.L.,Gonzalez, B. Multiple substrate recognition by yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase through phosphate clamping. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: The yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase DDP1 is a Nudix enzyme with pyrophosphatase activity on diphosphoinositides, dinucleotides, and polyphosphates. These substrates bind to diverse protein targets and participate in signaling and metabolism, being essential for energy and phosphate homeostasis, ATPase pump regulation, or protein phosphorylation. An exhaustive structural study of DDP1 in complex with multiple ligands related to its three diverse substrate classes is reported. This allowed full characterization of the DDP1 active site depicting the molecular basis for endowing multisubstrate abilities to a Nudix enzyme, driven by phosphate anchoring following a defined path. This study, combined with multiple enzyme variants, reveals the different substrate binding modes, preferences, and selection. Our findings expand current knowledge on this important structural superfamily with implications extending beyond inositide research. This work represents a valuable tool for inhibitor/substrate design for DDP1 and orthologs as potential targets to address fungal infections and other health concerns. PubMed: 33893105DOI: 10.1126/sciadv.abf6744 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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