Proteopedia:Featured JRN/2: Difference between revisions
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<tr><td><div class="scrolling"> | <tr><td><div class="scrolling">'''Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases.'''<br> | ||
''IB Tomasic, MC Metcalf, AI Guce, NE Clark, SC Garman''. J. Biol. Chem. 2010 doi: [http://dx.doi.org/10.1074/jbc.M110.118588 10.1074/jbc.M110.118588]<br> | ''IB Tomasic, MC Metcalf, AI Guce, NE Clark, SC Garman''. J. Biol. Chem. 2010 doi: [http://dx.doi.org/10.1074/jbc.M110.118588 10.1074/jbc.M110.118588]<br> | ||
The human lysosomal enzymes α-galactosidase and α-N-acetylgalactosaminidase share 46% amino acid sequence identity and have similar folds. Using a rational protein engineering approach, we interconverted the enzymatic specificity of α-GAL and α-NAGAL. The engineered α-GAL retains the antigenicity but has acquired the enzymatic specificity of α-NAGAL. Conversely, the engineered α-NAGAL retains the antigenicity but has acquired the enzymatic specificity of the α-GAL enzyme. Comparison of the crystal structures of the designed enzyme to the wild-type enzymes shows that active sites 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. | The human lysosomal enzymes α-galactosidase and α-N-acetylgalactosaminidase share 46% amino acid sequence identity and have similar folds. Using a rational protein engineering approach, we interconverted the enzymatic specificity of α-GAL and α-NAGAL. The engineered α-GAL retains the antigenicity but has acquired the enzymatic specificity of α-NAGAL. Conversely, the engineered α-NAGAL retains the antigenicity but has acquired the enzymatic specificity of the α-GAL enzyme. Comparison of the crystal structures of the designed enzyme to the wild-type enzymes shows that active sites 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. | ||