View source for 6slr


==Structure of saposin B in complex with atovaquone==
<StructureSection load='6slr' size='340' side='right'caption='[[6slr]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6slr]] is a 3 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=6SLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SLR 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]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AOQ:2-[TRANS-4-(4-CHLOROPHENYL)CYCLOHEXYL]-3-HYDROXYNAPHTHALENE-1,4-DIONE'>AOQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6slr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slr OCA], [https://pdbe.org/6slr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6slr RCSB], [https://www.ebi.ac.uk/pdbsum/6slr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6slr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SAP_HUMAN SAP_HUMAN] Defects in PSAP are the cause of combined saposin deficiency (CSAPD) [MIM:[https://omim.org/entry/611721 611721]; also known as prosaposin deficiency. CSAPD is due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.<ref>PMID:1371116</ref> <ref>PMID:11309366</ref>   Defects in PSAP saposin-B region are the cause of leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM:[https://omim.org/entry/249900 249900]. MLD-SAPB is an atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotr regression, seizures, cognitive decline and spastic quadriparesis.  Defects in PSAP saposin-C region are the cause of atypical Gaucher disease (AGD) [MIM:[https://omim.org/entry/610539 610539]. Affected individuals have marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease, a lysosomal storage disorder.<ref>PMID:2060627</ref> <ref>PMID:17919309</ref>   Defects in PSAP saposin-A region are the cause of atypical Krabbe disease (AKRD) [MIM:[https://omim.org/entry/611722 611722]. AKRD is a disorder of galactosylceramide metabolism. AKRD features include progressive encephalopathy and abnormal myelination in the cerebral white matter resembling Krabbe disease.<ref>PMID:15773042</ref>   Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
== Function ==
[https://www.uniprot.org/uniprot/SAP_HUMAN SAP_HUMAN] The lysosomal degradation of sphingolipids takes place by the sequential action of specific hydrolases. Some of these enzymes require specific low-molecular mass, non-enzymic proteins: the sphingolipids activator proteins (coproteins).  Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.  Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.  Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Doyle R]]
[[Category: Milliken B]]
[[Category: Zubieta C]]