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Aspartate 351 of estrogen receptor alpha is not crucial for the antagonist activity of antiestrogens

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dc.contributor.author Anghel, S. I. en_US
dc.contributor.author Perly, V. en_US
dc.contributor.author Melancon, G. en_US
dc.contributor.author Barsalou, A. en_US
dc.contributor.author Chagnon, S. en_US
dc.contributor.author Rosenauer, A. en_US
dc.contributor.author Miller, W. H., Jr. en_US
dc.contributor.author Mader, S. en_US
dc.date.accessioned 2006-06-19T17:41:07Z
dc.date.available 2006-06-19T17:41:07Z
dc.date.issued 2000-07 en_US
dc.identifier.citation J Biol Chem 275, 20867-72 (2000) en_US
dc.identifier.uri http://hdl.handle.net/1807.1/66
dc.description This article is hosted on a website external to the CBCRA Open Access Archive. Selecting “View/Open” below will launch the full-text article in another browser window.
dc.description.abstract The antagonist activity of antiestrogens is due to the presence of a long carbon side chain at positions 7alpha or 11beta or equivalent on their steroid or steroid-like skeletons. These side chains establish hydrophobic interactions with amino acids of the estrogen receptor alpha (ERalpha) ligand binding domain. In addition, a hydrogen bond formed between amino acid Asp-351 and the tertiary amine present at the end of the side chain of partial antiestrogens is considered to be crucial for their antiestrogenicity. Here, we have investigated the role of Asp-351 in antiestrogen action in transiently transfected HeLa and MDA-MB-231 cells. Our results indicate that disruption of the negative charge at position 351 does not increase the agonist activity of partial antiestrogens and thus that the hydrogen bond with the antiestrogen side chain is not determinant in positioning the side chain in an antagonist position. The negative charge at position 351 was not required for transcriptional activity in the presence of hormone, but its presence was necessary for basal activity of the wild-type receptor and constitutive activities of mutants L536P and Y537A, suggesting a role of Asp-351 in stabilizing the active conformation of ERalpha. This stabilizing role of Asp-351 could be due to interaction of Asp-351 with the amide group of the peptide bond between Leu-539 and Leu-540 in helix 12 observed in the active conformation of the ERalpha ligand binding domain. en_US
dc.description.provenance Made available in DSpace on 2006-06-19T17:41:07Z (GMT). No. of bitstreams: 1 Anghel.2000.20867.html: 415 bytes, checksum: ec2dde1cf4e44f9a1e57ef5f902e0b11 (MD5) Previous issue date: 2000-07 en
dc.format.extent 415 bytes
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dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology en_US
dc.relation.uri http://www.asbmb.org/ en_US
dc.title Aspartate 351 of estrogen receptor alpha is not crucial for the antagonist activity of antiestrogens en_US
dc.type Article en_US

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