2BCD

X-ray crystal structure of Protein Phosphatase-1 with the marine toxin motuporin bound

2BCD の概要

• エントリーDOI: 10.2210/pdb2bcd/pdb
• 関連するPDBエントリー: 2BDX
• 関連するBIRD辞書のPRD_ID: PRD_000213
• 分子名称: Serine/threonine protein phosphatase PP1-gamma catalytic subunit, MOTUPORIN, BETA-MERCAPTOETHANOL, ... (5 entities in total)
• 機能のキーワード: protein phosphtase, natural product inhibitors, motuporin, nodularin, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P36873
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38412.47

構造登録者

Maynes, J.T.,Luu, H.A.,Cherney, M.M.,Andersen, R.J.,Williams, D.,Holmes, C.F.,James, M.N. (登録日: 2005-10-19, 公開日: 2006-01-17, 最終更新日: 2023-11-15)

主引用文献

Maynes, J.T.,Luu, H.A.,Cherney, M.M.,Andersen, R.J.,Williams, D.,Holmes, C.F.,James, M.N.
Crystal Structures of Protein Phosphatase-1 Bound to Motuporin and Dihydromicrocystin-LA: Elucidation of the Mechanism of Enzyme Inhibition by Cyanobacterial Toxins.
J.Mol.Biol., 356:111-120, 2006

PubMed Abstract: The microcystins and nodularins are tumour promoting hepatotoxins that are responsible for global adverse human health effects and wildlife fatalities in countries where drinking water supplies contain cyanobacteria. The toxins function by inhibiting broad specificity Ser/Thr protein phosphatases in the host cells, thereby disrupting signal transduction pathways. A previous crystal structure of a microcystin bound to the catalytic subunit of protein phosphatase-1 (PP-1c) showed distinct changes in the active site region when compared with protein phosphatase-1 structures bound to other toxins. We have elucidated the crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (gamma isoform). The atomic structures of these complexes reveal the structural basis for inhibition of protein phosphatases by these toxins. Comparisons of the structures of the cyanobacterial toxin:phosphatase complexes explain the biochemical mechanism by which microcystins but not nodularins permanently modify their protein phosphatase targets by covalent addition to an active site cysteine residue.

PubMed: 16343532
DOI: 10.1016/j.jmb.2005.11.019

実験手法

X-RAY DIFFRACTION (2.1 Å)