title: [Lysosomal hydrolases have specific conformational domains for acquisition of mannose-6-phosphate].
abstract: In many mammalian cells, the transport of newly synthesized or externally added lysosomal enzymes to lysosomes is depend on their specific recognition by receptors for mannose 6-phosphate (Man-6-P). The physiological importance of this pathway was confirmed by the finding that fibroblasts from patients with mucolipidosis type II (ML-II ; I - cell disease) fail to phosphorylate mannose residues on their newly synthesized lysosomal enzymes, which results in the secretion of a large percentage of their acid hydrolases into the culture medium. However, lysosomal enzymes themselves do not contain the any consensus amino acid sequences for acquiring the Man-6-P recognition marker. Kornfeld et al revealed using cathepsin D-pepsinogen chimera proteins that UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase recognizes not only oligosaccharides but also the three-dimensional structure of the lysosomal enzymes when transfers N-acetylglucosamine-1-phosphate to lysosomal acid hydrolases.
authors.affiliation: Faculty of Pharmacautical Sciences, Kyusyu University.
authors.forename: M
authors.initials: M
authors.lastname: Himeno
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002402:Cathepsin D; D006801:Humans; D006867:Hydrolases / Q000737:chemistry*; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D017527:Receptor, IGF Type 2; D017855:Transferases (Other Substituted Phosphate Groups)
chemical_list: D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D017855:Transferases (Other Substituted Phosphate Groups); C030012:UDP-N-acetylglucosamine-lysosomal-enzyme-N-acetylglucosaminephosphotransferase; D006867:Hydrolases; D002402:Cathepsin D