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6y6t

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Current revision (13:20, 24 January 2024) (edit) (undo)
 
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==Mouse Galactocerebrosidase complexed with galacto-noeurostegine GNS at pH 4.6==
==Mouse Galactocerebrosidase complexed with galacto-noeurostegine GNS at pH 4.6==
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<StructureSection load='6y6t' size='340' side='right'caption='[[6y6t]]' scene=''>
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<StructureSection load='6y6t' size='340' side='right'caption='[[6y6t]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y6T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y6T FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6y6t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y6T FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y6t OCA], [http://pdbe.org/6y6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y6t RCSB], [http://www.ebi.ac.uk/pdbsum/6y6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y6t ProSAT]</span></td></tr>
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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]] 2.25&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ODW:(1~{R},2~{S},3~{S},4~{R},5~{R})-4-(hydroxymethyl)-8-azabicyclo[3.2.1]octane-1,2,3-triol'>ODW</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=6y6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y6t OCA], [https://pdbe.org/6y6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y6t RCSB], [https://www.ebi.ac.uk/pdbsum/6y6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y6t ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GALC_MOUSE GALC_MOUSE] Defects in Galc are the cause of the 'twitcher' phenotype; an autosomal recessive leukodystrophy similar to the human disease (Krabbe disease). This deficiency results in the insufficient catabolism of several galactolipids that are important in the production of normal myelin.
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== Function ==
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[https://www.uniprot.org/uniprot/GALC_MOUSE GALC_MOUSE] Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon.<ref>PMID:8769874</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Competitive inhibitors of galactocerebrosidase (GALC) could be candidates for pharmacological chaperone therapy of patients with Krabbe disease. The known and selective nortropane-type iminosugar galacto-noeurostegine has been found to competitively inhibit GALC with K (i) = 7 muM at pH 4.6, which is 330-fold more potent than the analogous deoxynoeurostegine. It was shown through X-ray protein crystallography that galacto-noeurostegine binds to the active site of GALC in its bicyclic form.
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The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of beta-Galactocerebrosidase.,Viuff A, Salamone S, McLoughlin J, Deane JE, Jensen HH ACS Med Chem Lett. 2020 Dec 18;12(1):56-59. doi: 10.1021/acsmedchemlett.0c00377. , eCollection 2021 Jan 14. PMID:33488964<ref>PMID:33488964</ref>
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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 6y6t" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Galactosylceramidase|Galactosylceramidase]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Mus musculus]]
[[Category: Deane JE]]
[[Category: Deane JE]]
[[Category: McLoughlin J]]
[[Category: McLoughlin J]]

Current revision

Mouse Galactocerebrosidase complexed with galacto-noeurostegine GNS at pH 4.6

PDB ID 6y6t

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