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http://purl.uniprot.org/citations/23159880http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23159880http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23159880http://www.w3.org/2000/01/rdf-schema#comment"Lysosomal storage diseases are treated with human lysosomal enzymes produced in mammalian cells. Such enzyme therapeutics contain relatively low levels of mannose-6-phosphate, which is required to target them to the lysosomes of patient cells. Here we describe a method for increasing mannose-6-phosphate modification of lysosomal enzymes produced in yeast. We identified a glycosidase from C. cellulans that 'uncaps' N-glycans modified by yeast-type mannose-Pi-6-mannose to generate mammalian-type N-glycans with a mannose-6-phosphate substitution. Determination of the crystal structure of this glycosidase provided insight into its substrate specificity. We used this uncapping enzyme together with α-mannosidase to produce in yeast a form of the Pompe disease enzyme α-glucosidase rich in mannose-6-phosphate. Compared with the currently used therapeutic version, this form of α-glucosidase was more efficiently taken up by fibroblasts from Pompe disease patients, and it more effectively reduced cardiac muscular glycogen storage in a mouse model of the disease."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.org/dc/terms/identifier"doi:10.1038/nbt.2427"xsd:string
http://purl.uniprot.org/citations/23159880http://purl.org/dc/terms/identifier"doi:10.1038/nbt.2427"xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Geysens S."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Geysens S."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Callewaert N."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Callewaert N."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Tiels P."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Tiels P."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Van Hecke A."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Van Hecke A."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Vervecken W."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Vervecken W."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Remaut H."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Remaut H."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Piens K."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Piens K."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Nerinckx W."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Nerinckx W."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Stout J."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Stout J."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Hulpiau P."xsd:string
http://purl.uniprot.org/citations/23159880http://purl.uniprot.org/core/author"Hulpiau P."xsd:string