Linked Life Data

12359124

Source:http://linkedlifedata.com/resource/pubmed/id/12359124

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-10-2
pubmed:abstractText
Fabry disease is a lysosomal storage disease caused by deficiency in the enzyme alpha-galactosidase (alpha-GAL). To understand the molecular defects responsible for Fabry disease, we have collected more than 190 reported point and stop mutations and mapped them onto a model of human alpha-GAL based on the X-ray structure of the closely related enzyme alpha-N-acetylgalactosaminidase (alpha-NAGAL). The locations of the human alpha-GAL point mutations reveal two major classes of Fabry disease protein defects: active site mutations and folding mutations. Active site mutations reduce enzymatic activity by perturbing the active site without necessarily affecting the overall alpha-GAL structure. Folding mutations reduce the stability of alpha-GAL by disrupting its hydrophobic core. Examining the frequency of mutation around each alpha-GAL residue identifies the active site as a hotspot for mutations leading to Fabry disease. This study furthers our understanding of the structural basis for mutations leading to Fabry disease, from which new avenues for the treatment of lysosomal storage diseases may be developed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1096-7192
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3-11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Structural basis of Fabry disease.
pubmed:affiliation
Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA.garman@alpha.niaid.nih.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review