Linked Life Data

12804601

Source:http://linkedlifedata.com/resource/pubmed/id/12804601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-6-13
pubmed:abstractText
Changes in DNA methylation patterns play an important role in tumorigenesis. The DNA methyltransferase 1 (DNMT1) protein represents a major DNA methyltransferase activity in human cells and is therefore a prominent target for experimental cancer therapies. However, there are only few available inhibitors and their high toxicity and low specificity have so far precluded their broad use in chemotherapy. Based on the strong conservation of catalytic DNA methyltransferase domains we have used a homology modeling approach to determine the three-dimensional structure of the DNMT1 catalytic domain. Our results suggest an overall structural conservation with other DNA methyltransferases but also indicate local conformational differences. To prove the validity of our model we used it as a template to design a novel derivative of the known DNA methyltransferase inhibitor 5-azacytidine. The resulting compound (N4-fluoroacetyl-5-azacytidine) functioned as an efficient inhibitor of DNA methylation in human tumor cell lines and also provides novel opportunities for pharmacological applications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
306
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
558-63
pubmed:dateRevised
2009-4-28
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Establishment and functional validation of a structural homology model for human DNA methyltransferase 1.
pubmed:affiliation
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't