Linked Life Data

10777608

Source:http://linkedlifedata.com/resource/pubmed/id/10777608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2000-6-2
pubmed:abstractText
The DNA strand passage activity of eukaryotic topoisomerase II relies on a cascade of conformational changes triggered by ATP binding to the N-terminal domain of the enzyme. To investigate the interdomain communication between the ATPase and cleavage/religation domains of human topoisomerase IIalpha, we characterized a mutant enzyme that contains a deletion at the interface between the two domains, covering amino acids 350-407. The ATPase domain retained full activity with a rate of ATP hydrolysis that was severalfold higher than normal, but the ATPase activity was unaffected by DNA. The cleavage and religation activities of the enzyme were comparable with those of the wild-type enzyme both in the absence and presence of cancer chemotherapeutic agents. However, neither ATP nor a nonhydrolyzable ATP analog stimulated cleavage complex formation. Although both conserved domains retained full activity, the mutant enzyme was unable to coordinate these activities into strand passage. Our findings suggest that the normal conformational transitions occurring in the enzyme upon ATP binding are hampered or lacking in the mutant enzyme. Consistent with this hypothesis, the enzyme displayed an abnormal clamp closing activity. In summary, the region covering amino acids 350-407 in human topoisomerase IIalpha seems to be essential for correct interdomain communication and probably is involved in signaling ATP binding to the rest of the enzyme.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13041-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10777608-Adenosine Triphosphatases, pubmed-meshheading:10777608-Adenosine Triphosphate, pubmed-meshheading:10777608-Antigens, Neoplasm, pubmed-meshheading:10777608-Conserved Sequence, pubmed-meshheading:10777608-DNA, pubmed-meshheading:10777608-DNA, Superhelical, pubmed-meshheading:10777608-DNA Topoisomerases, Type II, pubmed-meshheading:10777608-DNA-Binding Proteins, pubmed-meshheading:10777608-Gene Deletion, pubmed-meshheading:10777608-Genetic Complementation Test, pubmed-meshheading:10777608-Humans, pubmed-meshheading:10777608-Hydrolysis, pubmed-meshheading:10777608-Isoenzymes, pubmed-meshheading:10777608-Mutagenesis, pubmed-meshheading:10777608-Plasmids, pubmed-meshheading:10777608-Protein Conformation, pubmed-meshheading:10777608-Protein Structure, Tertiary, pubmed-meshheading:10777608-Saccharomyces cerevisiae, pubmed-meshheading:10777608-Time Factors
pubmed:year
2000
pubmed:articleTitle
Communication between the ATPase and cleavage/religation domains of human topoisomerase IIalpha.
pubmed:affiliation
Department of Molecular and Structural Biology, University of Aarhus, C. F. Mollers Allé, Building 130, 8000 Arhus C, Denmark.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't