1zvr
From Proteopedia
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Crystal Structure of MTMR2 in complex with phosphatidylinositol 3,5-bisphosphate
Contents |
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 with EDO and 3PI as ligands. 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
Page seeded by OCA on Mon Nov 12 20:42:03 2007
