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More stable, more e...
More stable, more estrogenic: the SERM-ERα LBD complex
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- Gao, Li (author)
- KTH,Teoretisk kemi och biologi
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- Tu, Yaoquan (author)
- KTH,Teoretisk kemi och biologi
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Eriksson, Leif A. (author)
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(creator_code:org_t)
- Scientific Research Publishing, Inc. 2011
- 2011
- English.
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In: Journal of Biophysical Chemistry. - : Scientific Research Publishing, Inc.. - 2153-036X .- 2153-0378. ; 2:3, s. 233-243
- Related links:
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http://www.scirp.org...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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Abstract
Subject headings
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- Many synthetic selective estrogen receptor mo- dulators (SERMs) have been cocrystallized with the human estrogen receptor α ligand binding domain (ERα LBD). Despite stabilizing the same canonical inactive conformation of the LBD, most SERMs display different ligand-dependent pharmacological profiles. We show here that in-creased partial agonism of SERMs is associated with increased conformational stability of the SERM-LBD complexes, by investigation of dihy-drobenzoxathiin-based SERMs using molecular modelling techniques. Analyses of tamoxifen (TAM) and 4-hydroxytamoxifen (OHT) in complex with the LBD furthermore indicates that the conversion of TAM to OHT increases both the affinity to ERα and the partial agonism of the anti-cancer drug, which provides a plausible ex-planation of the counterintuitive results of TAM therapy.
Keyword
- Breast Cancer; Tamoxifen Resistance; Molecular Dynamics Simulations; Dihydrobenzoxathiin; SERM
Publication and Content Type
- ref (subject category)
- art (subject category)
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