3bqq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[SAP_HUMAN] Defects in PSAP are the cause of combined saposin deficiency (CSAPD) [MIM: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.[1][2] Defects in PSAP saposin-B region are the cause of leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM: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: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.[3][4] Defects in PSAP saposin-A region are the cause of atypical Krabbe disease (AKRD) [MIM:611722]. AKRD is a disorder of galactosylceramide metabolism. AKRD features include progressive encephalopathy and abnormal myelination in the cerebral white matter resembling Krabbe disease.[5] Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
Function
[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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Schnabel D, Schroder M, Furst W, Klein A, Hurwitz R, Zenk T, Weber J, Harzer K, Paton BC, Poulos A, et al.. Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. J Biol Chem. 1992 Feb 15;267(5):3312-5. PMID:1371116
↑Hulkova H, Cervenkova M, Ledvinova J, Tochackova M, Hrebicek M, Poupetova H, Befekadu A, Berna L, Paton BC, Harzer K, Boor A, Smid F, Elleder M. A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation. Hum Mol Genet. 2001 Apr 15;10(9):927-40. PMID:11309366
↑Schnabel D, Schroder M, Sandhoff K. Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease. FEBS Lett. 1991 Jun 17;284(1):57-9. PMID:2060627
↑Tylki-Szymanska A, Czartoryska B, Vanier MT, Poorthuis BJ, Groener JA, Lugowska A, Millat G, Vaccaro AM, Jurkiewicz E. Non-neuronopathic Gaucher disease due to saposin C deficiency. Clin Genet. 2007 Dec;72(6):538-42. Epub 2007 Oct 7. PMID:17919309 doi:https://dx.doi.org/10.1111/j.1399-0004.2007.00899.x
↑Spiegel R, Bach G, Sury V, Mengistu G, Meidan B, Shalev S, Shneor Y, Mandel H, Zeigler M. A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans. Mol Genet Metab. 2005 Feb;84(2):160-6. PMID:15773042
↑Popovic K, Prive GG. Structures of the human ceramide activator protein saposin D. Acta Crystallogr D Biol Crystallogr. 2008 May;64(Pt 5):589-94. Epub 2008, Apr 19. PMID:18453694 doi:https://dx.doi.org/10.1107/S0907444908003120
