View source for 2vt0


==X-ray structure of a conjugate with conduritol-beta-epoxide of acid-beta-glucosidase overexpressed in cultured plant cells==
<StructureSection load='2vt0' size='340' side='right'caption='[[2vt0]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vt0]] is a 2 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=2VT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VT0 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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBU:(1R,2R,3S,4S,5S,6S)-CYCLOHEXANE-1,2,3,4,5,6-HEXOL'>CBU</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2vt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vt0 OCA], [https://pdbe.org/2vt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vt0 RCSB], [https://www.ebi.ac.uk/pdbsum/2vt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vt0 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GBA1_HUMAN GBA1_HUMAN] Gaucher disease type 3;Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome;Gaucher disease type 1;Hereditary late-onset Parkinson disease;Gaucher disease type 2;Fetal Gaucher disease;NON RARE IN EUROPE: Dementia with Lewy body;NON RARE IN EUROPE: Parkinson disease. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry. Perinatal lethal Gaucher disease is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.<ref>PMID:10352942</ref>   Disease susceptibility may be associated with variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GBA1_HUMAN GBA1_HUMAN] Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose (PubMed:15916907, PubMed:24211208, PubMed:32144204, PubMed:9201993). Plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204). GlcCer containing mono-unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (PubMed:24211208). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (Probable) (PubMed:26724485). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (PubMed:24211208, PubMed:26724485). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers (PubMed:32144204). Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside (PubMed:33361282).<ref>PMID:15916907</ref> <ref>PMID:19279011</ref> <ref>PMID:24211208</ref> <ref>PMID:26724485</ref> <ref>PMID:27378698</ref> <ref>PMID:32144204</ref> <ref>PMID:33361282</ref> <ref>PMID:9201993</ref> <ref>PMID:32144204</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/vt/2vt0_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2vt0 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
In mammalian cells, glucosylceramide (GlcCer), the simplest glycosphingolipid, is hydrolyzed by the lysosomal enzyme acid beta-glucosidase (GlcCerase). In the human metabolic disorder Gaucher disease, GlcCerase activity is significantly decreased owing to one of approximately 200 mutations in the GlcCerase gene. The most common therapy for Gaucher disease is enzyme replacement therapy (ERT), in which patients are given intravenous injections of recombinant human GlcCerase; the Genzyme product Cerezyme has been used clinically for more than 15 years and is administered to approximately 4000 patients worldwide. Here we review the crystal structure of Cerezyme and other recombinant forms of GlcCerase, as well as of their complexes with covalent and non-covalent inhibitors. We also discuss the stability of Cerezyme, which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease.

Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.,Kacher Y, Brumshtein B, Boldin-Adamsky S, Toker L, Shainskaya A, Silman I, Sussman JL, Futerman AH Biol Chem. 2008 Nov;389(11):1361-9. PMID:18783340<ref>PMID:18783340</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vt0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acid-beta-glucosidase 3D structures|Acid-beta-glucosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aviezer D]]
[[Category: Brumshtein B]]
[[Category: Futerman AH]]
[[Category: Greenblatt HM]]
[[Category: Shaaltiel Y]]
[[Category: Silman I]]
[[Category: Sussman JL]]