| Added by | informatique.ircm |
|---|---|
| Group name | Informatique |
| Item Type | Journal Article |
| Title | Differential interactions of estrogens and antiestrogens at the 17 beta-hydroxyl or counterpart hydroxyl with histidine 524 of the human estrogen receptor alpha |
| Creator | Aliau et al. |
| Author | S. Aliau |
| Author | H. Mattras |
| Author | E. Richard |
| Author | J. C. Bonnafous |
| Author | J. L. Borgna |
| Abstract | We investigated the role of H524 of the human estrogen receptor alpha (ERalpha) for the binding of various estrogens [estradiol (E(2)), 3-deoxyestradiol (3-dE(2)), and 17beta-deoxyestradiol (17beta-dE(2))] and antiestrogens [4-hydroxytamoxifen (OHT), RU 39 411 (RU), and raloxifene (Ral)], which possess the 17beta-hydroxyl or counterpart hydroxyl (designated: 17beta/c-OH), with the exception of 17beta-dE(2) and OHT. The work involved a comparison of the binding affinities of these ligands for wild-type and H524 mutant ERs, modified or not with diethyl pyrocarbonate (DEPC), a selective histidine reagent. Alanine substitution of H524 did not significantly change the association affinity constant (relative to OHT) of 17beta-dE(2), whereas those of RU, Ral, E(2), and 3-dE(2) were decreased 3-fold, 14-fold, 24-fold, and 49-fold, respectively. Values of the two ligands available in radiolabeled form (E(2) and OHT) were correlated with the dissociation rate constants, which were increased 250-fold and 2-fold, respectively. The action of DEPC on wild-type ER led to a homogeneous ER population which still bound antiestrogens and 17beta-dE(2) with practically unchanged affinities (less than 4-fold decreases in relative affinity constants), while E(2) and 3-dE(2) displayed markedly decreased affinities (56-fold decrease for E(2)). Conversely, DEPC treatment of H524A mutant ER did not induce marked decreases in the relative affinities of any of the checked compounds (decreases wild-type ER) and very weakly protected H524A ER. Molecular modeling was tentatively used to interpret the biochemical results. |
| Publication | Biochemistry |
| Volume | 41 |
| Issue | 25 |
| Pages | 7979-88 |
| Date | Jun 25 2002 |
| Tags | Alanine/genetics, Amino Acid Substitution/genetics, Animals, Binding Sites/genetics, Comparative Study, COS Cells, Diethyl Pyrocarbonate/chemistry, Estradiol/*analogs & derivatives/chemistry/metabolism, Estrogen Receptor Modulators/chemistry/*metabolism, Estrogens/chemistry/*metabolism, Histidine/genetics/*metabolism, Hydroxyl Radical/chemistry/*metabolism, inhibitors/chemistry/genetics/*metabolism, Ligands, Raloxifene/chemistry/metabolism, Receptors, Estrogen/antagonists &, Support, Non-U.S. Gov't, Tamoxifen/*analogs & derivatives/chemistry/metabolism |
| Date Added | 2019/12/19 - 16:59:45 |
| Date Modified | 2019/12/19 - 16:59:45 |
| Notes and Attachments | (Note) (Note) query (Attachment) |
Institut de Recherche en Cancérologie de
