1ZVR

Crystal Structure of MTMR2 in complex with phosphatidylinositol 3,5-bisphosphate

1ZVR の概要

• エントリーDOI: 10.2210/pdb1zvr/pdb
• 関連するPDBエントリー: 1ZSQ
• 分子名称: Myotubularin-related protein 2, 1,2-ETHANEDIOL, (1S)-2-(1-HYDROXYBUTOXY)-1-{[(HYDROXY{[(2R,3S,5R,6S)-2,4,6-TRIHYDROXY-3,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL)OXY]METHYL}ETHYL BUTYRATE, ... (4 entities in total)
• 機能のキーワード: protein-phosphoinositide complex, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q13614
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61926.98

構造登録者

Begley, M.J.,Taylor, G.S.,Brock, M.A.,Ghosh, P.,Woods, V.L.,Dixon, J.E. (登録日: 2005-06-02, 公開日: 2006-01-31, 最終更新日: 2023-08-23)

主引用文献

Begley, M.J.,Taylor, G.S.,Brock, M.A.,Ghosh, P.,Woods, V.L.,Dixon, J.E.
Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase
Proc.Natl.Acad.Sci.Usa, 103:927-932, 2006

PubMed Abstract: Myotubularins, a large family of catalytically active and inactive proteins, belong to a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as physiological substrates. Here, by integrating crystallographic and deuterium-exchange mass spectrometry studies of human myotubularin-related protein-2 (MTMR2) in complex with phosphoinositides, we define the molecular basis for this unique substrate specificity. Phosphoinositide substrates bind in a pocket located on a positively charged face of the protein, suggesting an electrostatic mechanism for membrane targeting. A flexible, hydrophobic helix makes extensive interactions with the diacylglycerol moieties of substrates, explaining the specificity for membrane-bound phosphoinositides. An extensive H-bonding network and charge-charge interactions within the active site pocket determine phosphoinositide headgroup specificity. The conservation of these specificity determinants within the active, but not the inactive, myotubularins provides insight into the functional differences between the active and inactive members.

PubMed: 16410353
DOI: 10.1073/pnas.0510006103

実験手法

X-RAY DIFFRACTION (1.98 Å)