7AUM

Yeast Diphosphoinositol Polyphosphate Phosphohydrolase DDP1 in complex with 5-PCF2Am-InsP5

7AUM の概要

• エントリーDOI: 10.2210/pdb7aum/pdb
• 関連するPDBエントリー: 7AUI 7AUJ 7AUK 7AUL
• 分子名称: Diphosphoinositol polyphosphate phosphohydrolase DDP1, (1,1-difluoro-2-oxo-2-{[(1s,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl]amino}ethyl)phosphonic acid (3 entities in total)
• 機能のキーワード: inositol, pp-insp, pyrophosphatase, polyphosphate, diadenosine polyphosphate, ddp1, nudix, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22549.78

構造登録者

Marquez-Monino, M.A.,Gonzalez, B. (登録日: 2020-11-03, 公開日: 2021-05-19, 最終更新日: 2024-01-31)

主引用文献

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

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: 33893105
DOI: 10.1126/sciadv.abf6744

実験手法

X-RAY DIFFRACTION (2.07 Å)