Linked Life Data

12208137

Source:http://linkedlifedata.com/resource/pubmed/id/12208137

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-9-4
pubmed:abstractText
Impairment of the human enzyme galactose-1-P uridylyltransferase (hGALT) results in the potentially lethal disorder, galactosemia. One of the fundamental questions with regard to this dimeric enzyme involves the possible influence of patient mutations on heterodimer formation and activity. Indeed, considering that many if not most galactosemia patients are compound heterozygotes, this is an issue of clinical as well as basic science interest. We have utilized a yeast expression system for the human enzyme to test whether each of a small number of mutations in hGALT (S135L, F171S, F171W, Q188R, N314D, and R333W) impact either heterodimer formation or function. Our results clearly demonstrate that while a majority of the alleles tested show precisely random patterns of subunit assortment, two deviate slightly but significantly from this pattern. Similarly, while some heterodimers exhibit apparent independence of subunit activity, others do not. These data not only demonstrate that common patient mutations in hGALT can influence both heterodimer formation and function in heterozygotes, they further raise the question of whether such interactions may also occur between different mutant alleles in compound heterozygotes (i.e., patients). Indeed, such influences may underlie some of the biochemical and clinical heterogeneity observed in the galactosemia patient population.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1096-7192
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
319-26
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Impact of patient mutations on heterodimer formation and function in human galactose-1-P uridylyltransferase.
pubmed:affiliation
Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.