Homology of lysosomal enzymes and related proteins: prediction of posttranslational modification sites including phosphorylation of mannose and potential epitopic and substrate binding sites in the alpha- and beta-subunits of hexosaminidases, alpha-glucosidase, and rabbit and human isomaltase.
Recently developed computer programs, including secondary structure and epitopic site predictions, have been used to align lysosomal proteins for maximum homology, based on conservative interchanges, and the aligned sequences have been searched for potential sites for posttranslational modification, glycosylation, and binding and catalysis of substrate. The homology and prediction of the posttranslational modification of the alpha- and beta-subunits of hexosaminidase is in good agreement with previous observations, and an explanation of the differing substrate specificities of the two subunits is advanced. We show that the striking homology between alpha-glucosidase and isomaltase is reflected in the apparent conservation of the active site in both enzymes. Nonhomologous regions have been examined in detail in a search for binding sites for glycogen and maltose, and two such sites have been tentatively identified. A highly redundant consensus sequence for the phosphorylation of mannose in lysosomal proteins, YXX(Y, W, or F), is suggested.
Barnes
A K
AK
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, United Kingdom.
Wynn
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D000939:Epitopes; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008358:Mannose / Q000378:metabolism*; D008969:Molecular Sequence Data; D009834:Oligo-1,6-Glucosidase / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D000520:alpha-Glucosidases / Q000378:metabolism*
D000939:Epitopes; D010770:Phosphotransferases; D006026:Glycoside Hydrolases; D006596:Hexosaminidases; D009834:Oligo-1,6-Glucosidase; D000520:alpha-Glucosidases; D008358:Mannose