Linked Life Data

8180165

Source:http://linkedlifedata.com/resource/pubmed/id/8180165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1994-6-10
pubmed:abstractText
The kinetic mechanism of the human platelet S-adenosyl-L-methionine (AdoMet)-linked isoprenylated protein methyltransferase was studied and determined to be ordered bibi. AdoMet binds first, and S-adenosyl-L-homocysteine (AdoHcy) departs last. Simple N-acetylated farnesylated cysteine analogs, such as N-acetyl-S-farnesyl-L-cysteine (AFC), are excellent substrates for the enzyme. Although many N-acetylated farnesylated cysteine analogs are excellent substrates for the enzyme, analogs with bulky moieties adjacent to the farnesylcysteine are neither substrates nor inhibitors of the enzyme. Two molecules of this class, N-benzoyl-S-farnesyl-L-cysteine (BzFC) and N-pivaloyl-S-farnesyl-L-cysteine (PFC) are useful in sorting out the putative physiological role of the methyltransferase in mediating human platelet aggregation because their pharmacological activities are unlinked to methyltransferase inhibition. When studied as inhibitors of platelet aggregation, the analogs are as active, or more active, than bona fide methyltransferase inhibitors of similar structure. Therefore, although it is possible that methyltransferase inhibitors, such as AFC, inhibit the enzyme when applied to cells, the observed pharmacological effects appear to be unrelated to this blockade. The new FC analogs described here have revealed a new signal transduction target which will be of some interest to explore.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5414-20
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Mechanistic studies on human platelet isoprenylated protein methyltransferase: farnesylcysteine analogs block platelet aggregation without inhibiting the methyltransferase.
pubmed:affiliation
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.