Linked Life Data

9590298

Source:http://linkedlifedata.com/resource/pubmed/id/9590298

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-5-29
pubmed:abstractText
Mutations in cystathionine beta-synthase (CBS) are known to cause homocystinuria, a recessive disorder characterized by excessive levels of total homocysteine (tHcy) in plasma. The primary cause of mortality is thromboembolism induced by the excessive tHcy levels. Mild increases in tHcy levels are a significant risk factor in the development of vascular disease in the general population. This can result from heterozygosity at the CBS locus or polymorphic variation in other enzymes involved in homocysteine re-methylation. We report here that a mutation which deletes the carboxy-terminal 145 amino acids of CBS can functionally suppress the phenotype of several CBS mutant alleles found in homocystinurics when expressed in yeast. This C-terminal domain of CBS acts to inhibit enzymatic activity and is in turn regulated by S-adenosylmethionine (AdoMet), a positive effector of CBS. Our results indicate that most mutations found in homocystinurics do not cause dysfunction of the catalytic domain, but rather interfere with the activation of the enzyme. These findings suggest a new drug target to treat homocystinuria and homocysteine-related vascular disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-3
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Correction of disease-causing CBS mutations in yeast.
pubmed:affiliation
Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't