Source:http://linkedlifedata.com/resource/pubmed/id/21520340
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
2011-6-28
|
| pubmed:abstractText |
?-Galactosidase deficiency is a group of lysosomal lipid storage disorders with an autosomal recessive trait. It causes two clinically different diseases, G(M1) -gangliosidosis and Morquio B disease. It is caused by heterogeneous mutations in the GLB1 gene coding for the lysosomal acid ?-galactosidase. We have previously reported the chaperone effect of N-octyl-4-epi-?-valienamine (NOEV) on mutant ?-galactosidase proteins. In this study, we performed genotype analyses of patients with ?-galactosidase deficiency and identified 46 mutation alleles including 9 novel mutations. We then examined the NOEV effect on mutant ?-galactosidase proteins by using six strains of patient-derived skin fibroblast. We also performed mutagenesis to identify ?-galactosidase mutants that were responsive to NOEV and found that 22 out of 94 mutants were responsive. Computational structural analysis revealed the mode of interaction between human ?-galactosidase and NOEV. Moreover, we confirmed that NOEV reduced G(M1) accumulation and ameliorated the impairments of lipid trafficking and protein degradation in ?-galactosidase deficient cells. These results provided further evidence to NOEV as a promising chaperone compound for ?-galactosidase deficiency.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
1098-1004
|
| pubmed:author |
pubmed-author:AdachiKaoriK,
pubmed-author:BahrudinUdinU,
pubmed-author:HigakiKatsumiK,
pubmed-author:HisatomeIchiroI,
pubmed-author:IidaMasamiM,
pubmed-author:IkehataHirokiH,
pubmed-author:LiLinjingL,
pubmed-author:MatsudaJunichiroJ,
pubmed-author:NanbaEijiE,
pubmed-author:NinomiyaHaruakiH,
pubmed-author:OgawaSeiichiroS,
pubmed-author:OhnoKousakuK,
pubmed-author:OkuzawaSoichiroS,
pubmed-author:ParaguisonRubigilda CRC,
pubmed-author:SakakibaraYasubumiY,
pubmed-author:SuzukiYoshiyukiY,
pubmed-author:TakaiTomokoT,
pubmed-author:TakamuramAyumiA,
pubmed-author:TominagaLikaL,
pubmed-author:YamamotoKoichiK
|
| pubmed:copyrightInfo |
© 2011 Wiley-Liss, Inc.
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
32
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
843-52
|
| pubmed:meshHeading |
pubmed-meshheading:21520340-Animals,
pubmed-meshheading:21520340-Cells, Cultured,
pubmed-meshheading:21520340-Enzyme Stability,
pubmed-meshheading:21520340-Fibroblasts,
pubmed-meshheading:21520340-Gangliosidosis, GM1,
pubmed-meshheading:21520340-Gene Expression,
pubmed-meshheading:21520340-Genetic Vectors,
pubmed-meshheading:21520340-Hexosamines,
pubmed-meshheading:21520340-Humans,
pubmed-meshheading:21520340-Mice,
pubmed-meshheading:21520340-Mice, Inbred C57BL,
pubmed-meshheading:21520340-Mice, Knockout,
pubmed-meshheading:21520340-Mucopolysaccharidosis IV,
pubmed-meshheading:21520340-Mutation, Missense,
pubmed-meshheading:21520340-Protein Structure, Tertiary,
pubmed-meshheading:21520340-Structure-Activity Relationship,
pubmed-meshheading:21520340-beta-Galactosidase
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in ?-galactosidase deficiency.
|
| pubmed:affiliation |
Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishi-cho, Yonago, Japan. kh4060@med.tottori-u.ac.jp
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|