View source for 5nxb


==Mouse galactocerebrosidase in complex with saposin A==
<StructureSection load='5nxb' size='340' side='right'caption='[[5nxb]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nxb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5n8k 5n8k]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NXB 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]] 3.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5nxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxb OCA], [https://pdbe.org/5nxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nxb RCSB], [https://www.ebi.ac.uk/pdbsum/5nxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxb ProSAT]</span></td></tr>
</table>
== Disease ==
[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.
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase beta-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded.

The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.,Hill CH, Cook GM, Spratley SJ, Fawke S, Graham SC, Deane JE Nat Commun. 2018 Jan 11;9(1):151. doi: 10.1038/s41467-017-02361-y. PMID:29323104<ref>PMID:29323104</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nxb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galactosylceramidase|Galactosylceramidase]]
*[[Saposin|Saposin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Deane JE]]
[[Category: Graham SC]]
[[Category: Hill CH]]