1zvr
From Proteopedia
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|PDB= 1zvr |SIZE=350|CAPTION= <scene name='initialview01'>1zvr</scene>, resolution 1.98Å | |PDB= 1zvr |SIZE=350|CAPTION= <scene name='initialview01'>1zvr</scene>, resolution 1.98Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=3PI:(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'>3PI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= MTMR2, KIAA1073 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MTMR2, KIAA1073 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1zsq|1ZSQ]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvr OCA], [http://www.ebi.ac.uk/pdbsum/1zvr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zvr RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603557 603557]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Taylor, G S.]] | [[Category: Taylor, G S.]] | ||
[[Category: Woods, V L.]] | [[Category: Woods, V L.]] | ||
| - | [[Category: 3PI]] | ||
| - | [[Category: EDO]] | ||
[[Category: protein-phosphoinositide complex]] | [[Category: protein-phosphoinositide complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:42:22 2008'' |
Revision as of 22:42, 30 March 2008
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| , resolution 1.98Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | MTMR2, KIAA1073 (Homo sapiens) | ||||||
| Related: | 1ZSQ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of MTMR2 in complex with phosphatidylinositol 3,5-bisphosphate
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.
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
Page seeded by OCA on Mon Mar 31 01:42:22 2008
