1ZSQ
Crystal Structure of MTMR2 in complex with phosphatidylinositol 3-phosphate
Summary for 1ZSQ
Entry DOI | 10.2210/pdb1zsq/pdb |
Descriptor | Myotubularin-related protein 2, 1,2-ETHANEDIOL, 2-(BUTANOYLOXY)-1-{[(HYDROXY{[2,3,4,6-TETRAHYDROXY-5-(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL)OXY]METHYL}ETHYL BUTANOATE, ... (4 entities in total) |
Functional Keywords | protein-phospholipid complex, hydrolase |
Biological source | Homo sapiens (human) |
Cellular location | Cytoplasm: Q13614 |
Total number of polymer chains | 1 |
Total formula weight | 61907.05 |
Authors | Begley, M.J.,Taylor, G.S.,Brock, M.A.,Ghosh, P.,Woods, V.L.,Dixon, J.E. (deposition date: 2005-05-25, release date: 2006-01-31, Last modification date: 2023-08-23) |
Primary citation | 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 Cited by 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: 16410353DOI: 10.1073/pnas.0510006103 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
Download full validation report
