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1m7r

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Revision as of 10:31, 18 October 2017

Crystal Structure of Myotubularin-related Protein-2 (MTMR2) Complexed with Phosphate

Structural highlights

1m7r is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1lw3
Gene:	MTMR2 (HUMAN)
Activity:	Phosphatidylinositol-3-phosphatase, with EC number 3.1.3.64
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MTMR2_HUMAN] Defects in MTMR2 are the cause of Charcot-Marie-Tooth disease type 4B1 (CMT4B1) [MIM:601382]. CMT4B1 is a recessive, severe form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy and primary peripheral axonal neuropathy. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention, autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.^[1] ^[2]

Function

[MTMR2_HUMAN] Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in members of the myotubularin family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. The crystal structure of a representative member of this family, MTMR2, reveals a phosphatase domain that is structurally unique among PTPs. A series of mutants are described that exhibit altered enzymatic activity and provide insight into the specificity of myotubularin phosphatases toward phosphoinositide substrates. The structure also reveals that the GRAM domain, found in myotubularin family phosphatases and predicted to occur in approximately 180 proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. Finally, the MTMR2 structure will serve as a model for other members of the myotubularin family and provide a framework for understanding the mechanism whereby mutations in these proteins lead to disease.

Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome.,Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, Stuckey JA Mol Cell. 2003 Dec;12(6):1391-402. PMID:14690594^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, Monaco AP. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000 May;25(1):17-9. PMID:10802647 doi:10.1038/75542
↑ Nelis E, Erdem S, Tan E, Lofgren A, Ceuterick C, De Jonghe P, Van Broeckhoven C, Timmerman V, Topaloglu H. A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths. Neuromuscul Disord. 2002 Nov;12(9):869-73. PMID:12398840
↑ Kim SA, Vacratsis PO, Firestein R, Cleary ML, Dixon JE. Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4492-7. Epub 2003 Mar 31. PMID:12668758 doi:10.1073/pnas.0431052100
↑ Franklin NE, Taylor GS, Vacratsis PO. Endosomal targeting of the phosphoinositide 3-phosphatase MTMR2 is regulated by an N-terminal phosphorylation site. J Biol Chem. 2011 May 6;286(18):15841-53. doi: 10.1074/jbc.M110.209122. Epub 2011, Mar 3. PMID:21372139 doi:10.1074/jbc.M110.209122
↑ Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, Stuckey JA. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell. 2003 Dec;12(6):1391-402. PMID:14690594

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1m7r"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Myotubularin-related Protein-2 (MTMR2) Complexed with Phosphate==
 <StructureSection load='1m7r' size='340' side='right' caption='[[1m7r]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTMR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-3-phosphatase Phosphatidylinositol-3-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.64 3.1.3.64] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m7r OCA], [http://pdbe.org/1m7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m7r RCSB], [http://www.ebi.ac.uk/pdbsum/1m7r PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m7r OCA], [http://pdbe.org/1m7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m7r RCSB], [http://www.ebi.ac.uk/pdbsum/1m7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m7r ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m7r ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 1m7r" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Dual specificity phosphatase|Dual specificity phosphatase]]
 == References ==
 <references/>

1m7r

From Proteopedia

Revision as of 10:31, 18 October 2017

Crystal Structure of Myotubularin-related Protein-2 (MTMR2) Complexed with Phosphate

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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