Linked Life Data

3373483

Source:http://linkedlifedata.com/resource/pubmed/id/3373483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1988-6-30
pubmed:abstractText
The requirements for active-site binding of thymidylate synthase from three sources, Lactobacillus casei, murine leukemia L1210, and human lymphoblast (Molt/4F), were investigated by analyzing the binding of a series of 5-(p-substituted phenyl)-2'-deoxyuridylates (N1-substituted 5-aryl-2, 4-dioxopyrimidines) to the enzyme. Multiple regression analysis revealed that an increase in electron density of the heterocyclic ring and hydrophobic substituents enhance affinity. Correlations of biological results with spectral data indicated that higher electron densities at the oxygen atoms are responsible for increase in binding. These results support the presence of both a cationic binding site and a hydrophobic region. In addition, the results revealed an unusual reversal of electronic requirements for binding and catalysis. The formation of the binary complex is enhanced by electron-donating substituents, while the initial catalytic reaction, formation of the covalent ternary complex, is promoted and stabilized by electron-withdrawing substituents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1141-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Linear free energy relationship studies of enzyme active site binding: thymidylate synthase.
pubmed:affiliation
Department of Medicinal Chemistry, University of Kansas, Lawrence 66045.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't