View source for 3bqp


==Crystal Structure of Human Saposin D (orthorhombic)==
<StructureSection load='3bqp' size='340' side='right'caption='[[3bqp]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bqp]] 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=3BQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BQP 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3bqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bqp OCA], [https://pdbe.org/3bqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bqp RCSB], [https://www.ebi.ac.uk/pdbsum/3bqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bqp 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).
== 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/bq/3bqp_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=3bqp ConSurf].
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== Publication Abstract from PubMed ==
Saposin D is a sphingolipid activator protein required for the lysosomal breakdown of ceramide to a fatty acid and sphingosine by acid ceramidase. The crystal structure of saposin D has been determined in two different crystal forms, resulting in a total of six crystallographically independent views of this small 80-amino-acid protein. All of the structures are highly similar and reveal the monomeric form of the saposin fold previously seen in the crystal structures of saposins A and C. Saposin D is slightly more compact than the related saposins A and C owing to a slight repositioning of the 'stem' and 'hairpin' regions of the protein.

Structures of the human ceramide activator protein saposin D.,Popovic K, Prive GG Acta Crystallogr D Biol Crystallogr. 2008 May;64(Pt 5):589-94. Epub 2008, Apr 19. PMID:18453694<ref>PMID:18453694</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3bqp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Saposin|Saposin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Popovic K]]
[[Category: Prive GG]]