Linked Life Data

19631742

Source:http://linkedlifedata.com/resource/pubmed/id/19631742

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-5
pubmed:dateCreated
2009-11-2
pubmed:abstractText
The enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has become an important drug target for breast cancer because it catalyzes the interconversion of estrone to the biologically more potent estradiol which also plays a crucial role in the etiology of breast cancer. Patients with an increased expression of the 17beta-HSD1 gene have a significantly worse outcome than patients without. Inhibitors for 17beta-HSD1 are therefore included in therapy development. Here we have studied binding of 17beta-HSD1 to substrates and a number of inhibitors using NMR spectroscopy. Ligand observed NMR spectra show a strong pH dependence for the phytoestrogens luteolin and apigenin but not for the natural ligands estradiol and estrone. Moreover, NMR competition experiments show that the phytoestrogens do not replace the estrogens despite their similar inhibition levels in the in vitro assay. These results strongly support an additional 17beta-HSD1 binding site for phytoestrogens which is neither the substrate nor the co-factor binding site. Docking experiments suggest the dimer interface as a possible location. An additional binding site for the phytoestrogens may open new opportunities for the design of inhibitors, not only for 17beta-HSD1, but also for other family members of the short chain dehydrogenases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1879-1220
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Ligand-based NMR spectra demonstrate an additional phytoestrogen binding site for 17beta-hydroxysteroid dehydrogenase type 1.
pubmed:affiliation
HWB-NMR, CR UK Institute of Cancer Sciences, University of Birmingham, Birmingham, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't