Sandbox Reserved 385: Difference between revisions
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<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' /> | <Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' /> | ||
<ref> Bizzini B. Tetanus Toxin. Microbiological Reviews.1979 June;43(2):224-236.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281472/pdf/microrev00006-0112.pdf?tool=pmcentrez]</ref> | |||
<ref>PMID:11807088</ref> | |||
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== Tamoxifen and the Estrogen Receptor == | == Tamoxifen and the Estrogen Receptor == | ||
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth. | Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing <scene name='Sandbox_Reserved_385/Test_scene/1'>helices 3, 8, and 11</scene> to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth. | ||
== Tamoxifen, the Drug == | == Tamoxifen, the Drug == | ||
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells. | Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells. | ||
[[Image:estrogen.PNG|The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen.]] | [[Image:estrogen.PNG|The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen.]] | ||
==References== | |||
<references /> | |||