Linked Life Data

7040662

Source:http://linkedlifedata.com/resource/pubmed/id/7040662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1982-6-21
pubmed:abstractText
Adenosine 5'-triphosphate (ATP) derivatives of the types N6-R-ATP [R = (CH2)nNHCOCH2I, (CH2)nNHCO-(CH2)mNHCOCH2I, or (CH2)nCON(Me)(CH2)mN(Me)CO(CH2)nNHCOCH2I], N6-Me-N6-R-ATP [R = (CH2)nN-(Me)CO(CH2)mNHCOCH2I], and 8-R-ATP [R = NM(CH2)nNHCOCH2I] with 5--19 spacer atoms between N6 or C-8 and iodine have been evaluated as potential exo-ATP-site-directed reagents for phosphokinases. Substrate and inhibitor properties indicated that the compounds possessed affinity for the ATP sites of the muscle (M), kidney (K), and liver (L) isozymes of rat pyruvate kinase (PK), of E. coli thymidine kinase (TK), and of yeast hexokinase (HK) and rat KH I, II, and III isozymes. Tests for time-dependent loss of enzyme activity (inactivation) were performed under conditions in which a large proportion of each phosphokinase was present as an enzyme-inhibitor complex. No ATP-site-directed inactivations resulted when the M, L, or K isozymes of PK were exposed for 8 h, 22 degrees C, to 5 mM levels of 18 ATP derivatives or 6 analogous ADP derivatives or when yeast HK or rat KH I, II, or III was exposed for 6 h, 22 degrees C, to 5 mM levels of 28 ATP derivatives. Escherichia coli TK was inactivated by 6 of 25 ATP derivatives tested at 10 mM, 6 h, 0 degrees C; inactivation was slowed by MgATP in the case of N6-CH3-N6-R-ATP [R = (CH2)4N(CH3)CO(CH2)5NHCOCH2I]. Only 1% of 298 enzyme-inhibitor combinations exhibited ATP-site-directed inactivation, signifying that few suitably positioned and sufficiently reactive nucleophilic groups were present near the enzymic ATP sites. Studies have now shown that exo-active-site-directed reagents can act as isozyme- or species-selective enzyme inhibitors. The present survey indicates that in many cases such reagents may be difficult of access when data are not available regarding structural or physicochemical features of the target enzyme adjacent to its catalytic site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
386-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 5. Interactions of adenosine 5'-triphosphate derivatives with rat pyruvate kinases, Escherichia coli thymidine kinase, and yeast and rat hexokinases.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't