4r30

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(New page: '''Unreleased structure''' The entry 4r30 is ON HOLD Authors: Sankhala, R.S., Koksal, A.C., Cingolani, G. Description: Structure of human laforin dual specificity phosphatase domain)
Current revision (17:43, 20 September 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 4r30 is ON HOLD
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==Structure of human laforin dual specificity phosphatase domain==
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<StructureSection load='4r30' size='340' side='right'caption='[[4r30]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4r30]] is a 4 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=4R30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R30 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r30 OCA], [https://pdbe.org/4r30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r30 RCSB], [https://www.ebi.ac.uk/pdbsum/4r30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r30 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/EPM2A_HUMAN EPM2A_HUMAN] Lafora disease. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/EPM2A_HUMAN EPM2A_HUMAN] Has both dual-specificity protein phosphatase and glucan phosphatase activities. Together with the E3 ubiquitin ligase NHLRC1/malin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. Dephosphorylates phosphotyrosine, phosphoserine and phosphothreonine substrates in vitro. Has also been shown to dephosphorylate MAPT. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates. Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Also promotes proteasome-independent protein degradation through the macroautophagy pathway. Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1.<ref>PMID:11001928</ref> <ref>PMID:11220751</ref> <ref>PMID:16901901</ref> <ref>PMID:18070875</ref> <ref>PMID:18617530</ref> <ref>PMID:19036738</ref> <ref>PMID:20453062</ref> <ref>PMID:23624058</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The phosphatase laforin removes phosphate groups from glycogen during biosynthetic activity. Loss of function mutations in the gene encoding laforin is the predominant cause of Lafora disease (LD), a fatal form of progressive myoclonic epilepsy. Here, we used hybrid structural methods to determine the molecular architecture of human laforin. We found that laforin adopts a dimeric quaternary structure, topologically similar to the prototypical dual specificity phosphatase (DSP) VH1. The interface between laforin carbohydrate-binding module (CBM) and DSP domain generates an intimate substrate-binding crevice that allows for recognition and dephosphorylation of phosphomonoesters of glucose. We identify novel molecular determinants in laforin active site that help decipher the mechanism of glucan phosphatase activity.
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Authors: Sankhala, R.S., Koksal, A.C., Cingolani, G.
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Dimeric quaternary structure of human laforin.,Sankhala RS, Koksal AC, Ho L, Nitschke F, Minassian BA, Cingolani G J Biol Chem. 2014 Dec 23. pii: jbc.M114.627406. PMID:25538239<ref>PMID:25538239</ref>
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Description: Structure of human laforin dual specificity phosphatase domain
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4r30" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cingolani G]]
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[[Category: Koksal AC]]
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[[Category: Sankhala RS]]

Current revision

Structure of human laforin dual specificity phosphatase domain

PDB ID 4r30

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