| The effect of carbohydrate removal on stability and activity of saposin B. | |
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MedLine Citation:
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PMID: 8099782 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Saposin B is involved in the hydrolysis of sulfatides, GM1 ganglioside, globotriaosylceramide, and several other sphingolipids and glycerolipids by lysosomal hydrolases. Saposin B is one of four small glycoproteins (saposins) derived from prosaposin. The carbohydrate chain of saposin B was removed and deglycosylated saposin B was characterized and compared with native saposin B. Deglycosylated saposin B stimulated the enzymatic hydrolysis of ganglioside GM1 by acid beta-galactosidase and sulfatide by arylsulfatase A to the same extent as native saposin B. In addition deglycosylated saposin B bound sulfatide and GM1 ganglioside identical to native saposin B. The stability of native saposin B to proteolytic digestion was unchanged by deglycosylation. Neither native saposin B nor deglycosylated saposin B were hydrolyzed by trypsin, endoproteinase Glu-C (V-8), chymotrypsin, or a mixture of acid proteases isolated from human testis. Unlike its effect on metabolic stability, the carbohydrate chain appears to affect folding of saposin B. When native and deglycosylated saposin B were reduced under denaturing conditions and refolded under identical conditions examination of the refolded products indicated that each protein was refolded in a qualitatively different way. A human mutation in saposin B-deficient metachromatic leukodystrophy, in which its glycosylation site is eliminated, has been reported. Our observations suggest that instability of the mutated saposin B is not due to the absence of a protective effect of the carbohydrate chain on proteolysis, but is likely due to aberrant folding resulting from the absence of a carbohydrate chain. |
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Authors:
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M Hiraiwa; S Soeda; B M Martin; A L Fluharty; Y Hirabayashi; J S O'Brien; Y Kishimoto |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 303 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 1993 Jun |
Date Detail:
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Created Date: 1993-07-09 Completed Date: 1993-07-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 326-31 Citation Subset: IM |
Affiliation:
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Department of Neurosciences, University of California, San Diego, La Jolla 92093-0634. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Carbohydrates
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chemistry* Cerebroside-Sulfatase / metabolism Chromatography, High Pressure Liquid Drug Stability Electrophoresis, Polyacrylamide Gel G(M1) Ganglioside / metabolism Gaucher Disease / metabolism Glycoproteins / chemistry*, metabolism, pharmacology Glycosylation Humans Hydrolysis Saposins Sphingolipid Activator Proteins Spleen / chemistry Structure-Activity Relationship Sulfoglycosphingolipids / metabolism beta-Galactosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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NS-08682/NS/NINDS NIH HHS; NS-13559/NS/NINDS NIH HHS; NS-22655/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbohydrates; 0/Glycoproteins; 0/PSAP protein, human; 0/Saposins; 0/Sphingolipid Activator Proteins; 0/Sulfoglycosphingolipids; 37758-47-7/G(M1) Ganglioside; EC 3.1.6.8/Cerebroside-Sulfatase; EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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