View source for 1zvr


==Crystal Structure of MTMR2 in complex with phosphatidylinositol 3,5-bisphosphate==
<StructureSection load='1zvr' size='340' side='right'caption='[[1zvr]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zvr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZVR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvr OCA], [https://pdbe.org/1zvr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zvr RCSB], [https://www.ebi.ac.uk/pdbsum/1zvr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MTMR2_HUMAN MTMR2_HUMAN] Defects in MTMR2 are the cause of Charcot-Marie-Tooth disease type 4B1 (CMT4B1) [MIM:[https://omim.org/entry/601382 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.<ref>PMID:10802647</ref> <ref>PMID:12398840</ref> 
== Function ==
[https://www.uniprot.org/uniprot/MTMR2_HUMAN MTMR2_HUMAN] Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate.<ref>PMID:12668758</ref> <ref>PMID:21372139</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zv/1zvr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <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/main_output.php?pdb_ID=1zvr ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:16410353</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1zvr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Begley MJ]]
[[Category: Brock MA]]
[[Category: Dixon JE]]
[[Category: Ghosh P]]
[[Category: Taylor GS]]
[[Category: Woods VL]]