Intracellular receptors: Difference between revisions

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Alexander Berchansky

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 This <scene name='48/483891/Estrogen_kyle/8'>scene</scene> depicts the hydrophobic and hydrophilic residues of the estrogen receptor. The hydrophobic regions are primarily on the inside of the protein surrounding genistein shown in red.  Having the hydrophobic residues surrounding the binding pocket will stabilize the structure. The structure of this pocket is tertiary and do to the hydrophobic interactions inside the pocket and hydrophilic interactions on the outside help to stabilize this tertiary structure.  The <scene name='48/483891/Estrogen_kyle/16'>binding pocket</scene> is hydrophobic which means that an increase in lipophilicity would increase the ffinity for ligands which in this case is genistein. The genistein structure has 3 hydroxyl groups, an ether and an ester.  These 3 functional groups are polar and have many possibilities for hydrogen bonding. The His475 and Met336 residues in the binding pocket are capable of forming hydrogen bonds with genistein do to the many hydrogen bond forming functional groups. These residues are different from the residues found in ERα and so the selectivity of genistein is much greater for ERβ.
-Several others factors play a role in ERβ binding, one is steric effects around the binding pocket.  The shape of this pocket will create some selectivity based on the size of incoming ligands. Genistein is able to bind because it has the correct size as well as hydrophobic functional groups. If a large bulky ligand tries to bind to the receptor it may have a difficult time do to steric interactions.  Another factor is electronic effects such as conjugation which could interfere with binding as well.  Genistein is a conjugated system and because it has several oxygen atoms with electron lone pairs electron density could be shifted in a way to help it bind to the ERβ form giving reason to its greater selectivity than ERα.
+We can see the initial view of the complex. Upon visualizing the estrogen receptor in an arrow formation, <scene name='48/483891/Arrow_view/1'>arrow representation</scene>, the structure can be classified as parallel or anti-parallel. Here is the zoomed <scene name='48/483891/Hydrophobic_pocket/3'>primarily hydrophobic pocket</scene>.
-First, we can see the initial view of the complex. Upon visualizing the estrogen receptor in an arrow formation, <scene name='48/483891/Arrow_view/1'>arrow representation</scene>, the structure can be classified as parallel or anti-parallel. Here is the zoomed <scene name='48/483891/Hydrophobic_pocket/3'>primarily hydrophobic pocket</scene>.
 *[[Estrogen-related receptor]]
 <scene name='50/501401/Cv/4'>Binding of nuclear receptor corepressor 2 peptide and 4-hydroxytamoxifen</scene> to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and <scene name='50/501401/Cv/5'>tamoxifen</scene> are nestled between 4 alpha helices in the ERR active site.