Source:http://linkedlifedata.com/resource/pubmed/id/10507314
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1999-10-28
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pubmed:abstractText |
Steady-state levels and rates of DNA binding and release of wild-type and mutant topoisomerase I (Topo I) proteins were quantified by surface plasmon resonance analysis. The proteins were constructed and expressed as GST fusion proteins. The Topo I mutations analyzed were F361S, R362L and R364G, all altering a highly conserved region of wild-type eukaryotic Topo I. The R362L and R364G mutations resulted in much lower steady-state levels of DNA binding than wild-type. This was due to a large increase in the k(d). The F361S mutation increased the steady-state levels of the protein-DNA interaction by increasing the k(a) 2-fold, while having little effect on the k(d). The F361S mutation has been shown to confer resistance to camptothecin and its analogs. The camptothecin analog 9-aminocamptothecin decreased greatly the overall k(d) of the wild-type Topo I, but had little effect on the F361S mutant. Both the wild-type and the F361S mutant exhibited decreased steady-state levels in the presence of the drug, and this was attributable to decreased association.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/9-amino-20-camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0959-4973
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
647-53
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10507314-Antineoplastic Agents,
pubmed-meshheading:10507314-Camptothecin,
pubmed-meshheading:10507314-Catalysis,
pubmed-meshheading:10507314-DNA,
pubmed-meshheading:10507314-DNA Topoisomerases, Type I,
pubmed-meshheading:10507314-Mutation,
pubmed-meshheading:10507314-Structure-Activity Relationship
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pubmed:year |
1999
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pubmed:articleTitle |
Effects of mutations in the F361 to R364 region of topoisomerase I (Topo I), in the presence and absence of 9-aminocamptothecin, on the Topo I-DNA interaction.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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