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http://purl.uniprot.org/citations/20444686 | http://www.w3.org/2000/01/rdf-schema#comment | "The human lysosomal enzymes alpha-galactosidase (alpha-GAL, EC 3.2.1.22) and alpha-N-acetylgalactosaminidase (alpha-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of alpha-GAL and alpha-NAGAL. The engineered alpha-GAL (which we call alpha-GAL(SA)) retains the antigenicity of alpha-GAL but has acquired the enzymatic specificity of alpha-NAGAL. Conversely, the engineered alpha-NAGAL (which we call alpha-NAGAL(EL)) retains the antigenicity of alpha-NAGAL but has acquired the enzymatic specificity of the alpha-GAL enzyme. Comparison of the crystal structures of the designed enzyme alpha-GAL(SA) to the wild-type enzymes shows that active sites of alpha-GAL(SA) and alpha-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.118588"xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/author | "Clark N.E."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/author | "Garman S.C."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/author | "Metcalf M.C."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/author | "Guce A.I."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/author | "Tomasic I.B."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/pages | "21560-21566"xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/title | "Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases."xsd:string |
http://purl.uniprot.org/citations/20444686 | http://purl.uniprot.org/core/volume | "285"xsd:string |
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