Linked Life Data

3572977

Source:http://linkedlifedata.com/resource/pubmed/id/3572977

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1987-6-10
pubmed:abstractText
A synthesis is described of the title compound and its 5'S epimer, which are two-substrate adducts of adenosine 5'-triphosphate (ATP) and L-methionine (Met) in which the C(5')H2OP system in ATP is replaced by CH(R)CH2NHP [R = L-S(CH2)2CH(NH2)CO2H]. The 5'R epimer was a potent nonselective competitive inhibitor [averaged Ki = 0.32 microM; KM(ATP)/Ki = 440] vs. ATP of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase. It produced simple noncompetitive inhibition (averaged Ki = 2.7 microM) vs. Met with both variants. The 5'S epimer inhibited M-T competitively vs. ATP, but was 74-fold less effective than the 5'R epimer. Replacement of the homocysteine moiety in the 5'R epimer by hydrogen markedly reduced inhibitory potency, as indicated by Ki values of 14 microM for competitive inhibition vs. ATP and 580 microM for noncompetitive inhibition vs. Met with M-2. The data suggest that the 5'R epimer can interact simultaneously with two enzymic sites. Information on the kinetic mechanism of a human counterpart of M-2 and inhibitor properties of a previously studied Met-ATP adduct are consistent with the view that the two sites might resemble those that interact with the initial products of the reaction, S-adenosylmethionine and triphosphate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
888-94
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Isozyme-specific enzyme inhibitors. 13. S-[5'(R)-[(N-triphosphoamino)methyl]adenosyl]-L-homocysteine, a potent inhibitor of rat methionine adenosyltransferases.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't