Linked Life Data

12788103

Source:http://linkedlifedata.com/resource/pubmed/id/12788103

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-5
pubmed:abstractText
Arylsulfatase A (ARSA) is a lysosomal enzyme implicated in most cases of metachromatic leukodystrophy (MLD). The quaternary structure of ARSA is pH-dependent: at neutral pH, ARSA is a homodimeric protein; at lysosomal (acidic) pH, ARSA is homo-octameric. This dimer-octamer transition seems to be of major importance for the stability of the enzyme in the lysosomal milieu. Sedimentation analysis was used to study the oligomerization capacity of C300F and P425T-substituted ARSA, two MLD-associated forms of the enzyme displaying reduced lysosomal half-lives. P425T-ARSA displays a modest reduction in its octamerization capacity. In contrast, the C300F mutation strongly interferes with the octamerization process of ARSA but not with its dimerization capacity. Interestingly, a major fraction of dimeric ARSA-C300F is composed of covalently linked ARSA molecules, through a thiol-cleavable bond that probably involves Cys414 residues from each monomer. Our data support the notion that the reduced lysosomal half-life of some mutated forms of ARSA is related to deficient octamerization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
306
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
293-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T.
pubmed:affiliation
Unidade da Biologia do Lisossoma e do Peroxissoma do Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't