3E7B

Crystal Structure of Protein Phosphatase-1 Bound to the natural toxin inhibitor Tautomycin

3E7B の概要

• エントリーDOI: 10.2210/pdb3e7b/pdb
• 関連するPDBエントリー: 1FJM 1IT6 1JK7 2BCD 3E7A
• 分子名称: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, MANGANESE (II) ION, (2Z)-2-[(1R)-3-{[(1R,2S,3R,6S,7S,10R)-10-{(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undec-2-yl}-3,7-dihydroxy-2-methoxy-6-methyl-1-(1-methylethyl)-5-oxoundecyl]oxy}-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid, ... (8 entities in total)
• 機能のキーワード: protein phosphatase 1, tautomycin, molecular toxin, carbohydrate metabolism, cell cycle, cell division, glycogen metabolism, hydrolase, iron, manganese, metal-binding, phosphoprotein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P62136
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70516.64

構造登録者

Kelker, M.S.,Page, R.,Peti, W. (登録日: 2008-08-18, 公開日: 2008-11-04, 最終更新日: 2023-08-30)

主引用文献

Kelker, M.S.,Page, R.,Peti, W.
Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors
J.Mol.Biol., 385:11-21, 2009

PubMed Abstract: Protein phosphatase 1 occurs in all tissues and regulates many pathways, ranging from cell-cycle progression to carbohydrate metabolism. Many naturally occurring, molecular toxins modulate PP1 activity, though the exact mechanism of this differential regulation is not understood. A detailed elucidation of these interactions is crucial for understanding the cellular basis of phosphatase function and signaling pathways but, more importantly, they can serve as the basis for highly specific therapeutics, e.g. against cancer. We report the crystal structures of PP1 in complex with nodularin-R at 1.63 A and tautomycin at 1.70 A resolution. The PP1:nodularin-R complex was used to demonstrate the utility of our improved PP1 production technique, which produces highly active, soluble PP1. Tautomycin is one of the few toxins that reportedly preferentially binds PP1>PP2A. Therefore, the PP1:tautomycin structure is the first complex structure with a toxin with preferred PP1 specificity. Furthermore, since tautomycin is a linear non-peptide-based toxin, our reported structure will aid the design of lead compounds for novel PP1-specific pharmaceuticals.

PubMed: 18992256
DOI: 10.1016/j.jmb.2008.10.053

実験手法

X-RAY DIFFRACTION (1.7 Å)