Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chinese hamster ovary cells were transfected with a recombinant DNA containing the entire coding sequence of human lysosomal protective protein cDNA under the control of mouse metallothionein I promoter. Neomycin and methotrexate-resistant stably transformed cell lines expressing this protein were isolated. Immunoprecipitation of the product with antiserum against human placental protective protein-beta-galactosidase complex revealed a 52-kDa protective protein precursor, which was then processed to mature form, a heterodimer of 32- and 20-kDa polypeptides. The precursor secreted in the culture medium was taken up by the mannose 6-phosphate receptor system and restored acid carboxypeptidase, beta-galactosidase, and neuraminidase activities in galactosialidosis fibroblasts. The expressed protein showed a granular pattern in intracellular distribution, was fractionated at the density of lysosomes, and had serine esterase activities; acid carboxypeptidase at pH 5.6, esterase at pH 7.0, and carboxyl-terminal deamidase at pH 7.0. They were inhibited simultaneously by phenylmethylsulfonyl fluoride, N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone, or iodoacetamide. The acid carboxypeptidase activity of the purified monomeric mature protective protein was labile in vitro under the acidic condition. Saposins (sphingolipid activator proteins) stabilized the activity at micromolar level concentrations.
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PMID:Purification and characterization of human lysosomal protective protein expressed in stably transformed Chinese hamster ovary cells. 841 22

Galactosialidosis is a human autosomal recessive lysosomal storage disease caused by a genetic defect of protective protein/cathepsin A (PPCA). The patients in a Japanese family with the severe early-infantile form of galactosialidosis were revealed to be homozygous for the A1184-G transition in the PPCA gene in both alleles, which leads to the Y395C substitution. The acid carboxypeptidase (cathepsin A) and lysosomal neuraminidase activities were markedly decreased in cultured fibroblasts and chorionic villus cells derived from the patients, although the decrease in beta-galactosidase activity was less. Immunoblot and immunocytochemical analyses showed that neither the precursor nor the mature form of the PPCA gene product was present in the cultured cells. The Y395C mutation was revealed to cause the loss of the translated product, that determines the severity of the clinical phenotype.
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PMID:Protective protein/cathepsin A loss in cultured cells derived from an early-infantile form of galactosialidosis patients homozygous for the A1184-G transition (Y395C mutation). 963 45