1zvr | pdb_00001zvr
Crystal Structure of MTMR2 in complex with phosphatidylinositol 3,5-bisphosphate
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| 1zvr, resolution 1.98Å | |||||||||||||
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| Ligands: | EDO and 3PI | ||||||||||||
| Gene: | MTMR2, KIAA1073 (Homo sapiens) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
Disease
Known disease associated with this structure: Charcot-Marie-Tooth disease, type 4B1 OMIM:[603557]
About this Structure
1ZVR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase., Begley MJ, Taylor GS, Brock MA, Ghosh P, Woods VL, Dixon JE, Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):927-32. Epub 2006 Jan 12. PMID:16410353
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