1n69: Difference between revisions

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-{{Seed}}
-[[Image:1n69.png|left|200px]]
-<!--
+==Crystal structure of human saposin B==
-The line below this paragraph, containing "STRUCTURE_1n69", creates the "Structure Box" on the page.
+<StructureSection load='1n69' size='340' side='right'caption='[[1n69]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1n69]] 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=1N69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N69 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene></td></tr>
-{{STRUCTURE_1n69|  PDB=1n69  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n69 OCA], [https://pdbe.org/1n69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n69 RCSB], [https://www.ebi.ac.uk/pdbsum/1n69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n69 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/n6/1n69_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=1n69 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Saposin B is a small, nonenzymatic glycosphingolipid activator protein required for the breakdown of cerebroside sulfates (sulfatides) within the lysosome. The protein can extract target lipids from membranes, forming soluble protein-lipid complexes that are recognized by arylsulfatase A. The crystal structure of human saposin B reveals an unusual shell-like dimer consisting of a monolayer of alpha-helices enclosing a large hydrophobic cavity. Although the secondary structure of saposin B is similar to that of the known monomeric members of the saposin-like superfamily, the helices are repacked into a different tertiary arrangement to form the homodimer. A comparison of the two forms of the saposin B dimer suggests that extraction of target lipids from membranes involves a conformational change that facilitates access to the inner cavity.
-===Crystal structure of human saposin B===
+Crystal structure of saposin B reveals a dimeric shell for lipid binding.,Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Prive GG Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):38-43. Epub 2002 Dec 23. PMID:12518053<ref>PMID:12518053</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1n69" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12518053}}, adds the Publication Abstract to the page
+*[[Saposin|Saposin]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12518053 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_12518053}}
+__TOC__
+</StructureSection>
-==About this Structure==
-N69 is a 3 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N69 OCA].
-==Reference==
-<ref group="xtra">PMID:12518053</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Ahn, V E.]]
+[[Category: Large Structures]]
-[[Category: Faull, K F.]]
+[[Category: Ahn VE]]
-[[Category: Fluharty, A L.]]
+[[Category: Faull KF]]
-[[Category: Prive, G G.]]
+[[Category: Fluharty AL]]
-[[Category: Whitelegge, J P.]]
+[[Category: Prive GG]]
-[[Category: Glycosphingolipid activator protein]]
+[[Category: Whitelegge JP]]
-[[Category: Lipid binding protein]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 16:32:42 2009''