Sandbox 77: Difference between revisions

The <scene name='71/716548/5-ht1b/1'>5-HT1B receptor</scene> couples to G-protein alpha subunits Gi and Go. In the central nervous system, this receptor is an inhibitory presynaptic receptor that can alter the release of serotonin, as well as other neurotransmitters, from the presynaptic neuron. The structure of this receptor includes <scene name='71/716548/5-ht1b/6'>7 transmembrane alpha-helices</scene>.<scene name='71/716548/5-ht1b/8'>The N-terminal tail</scene> of 5-HT1B is close to the ligand binding pocket suggesting some interaction with its ligand. <scene name='71/716548/5-ht1b/9'>The ligand binding pocket</scene>, also called the orthosteric binding pocket, is characterized as a cavity formed from residues of the 3rd, 5th, 6th, and 7th alpha helices and the 2nd extracellular loop. <ref name = "one" />

The <scene name='71/716548/5-ht2b_receptor/1'>5-HT2B receptor</scene> is important in utilizing serotonin signals to encourage proper development and continuing function of the cardiovascular system. Overexpression of 5-HT2B has been linked to congestive heart failure.<ref>Wiebke J, Schymura Y, Novoyatleva T, Kojonazarov B, Boehm M, Wietelmann A, Luitel H, Murmann K, Krompiec DR, Tretyn A, Pullamsetti SS, Weissmann N, Seeger W, Ghofrani HA, Schermuly RT. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure. Biomed Res Int. 2015; 2015: 438403. PMID:4312574 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312574]</ref> 5-HT2B utilizes the alpha Gq protein pathway which triggers intracellular cGMP production through activation of nictric-oxidase synthase (NOS).<ref>Nebigil, Etienne, Schaerlinger, Hickel, Launay, Maroteaux. ''Developmentally Regulated Serotonin 5-HT2B Receptors.'' [http://www.sciencedirect.com/science/article/pii/S0736574801000223 DOI: 10.1016/S0736-5748(01)00022-3]</ref> This receptor is also known for being the target of the drug LSD, which has similar structure to serotonin. <ref>Berumen LC, Rodriguez A, Miledi R, Gracia-Alcocer G. Serotonin Receptors in Hippocampus. ScientificWorldJournal. 2012;2012:823493. Epub 2012 May 2. PMID:3353568 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353568/]</ref> The structure of this receptor is much like that of 5-HT1B, however significant differences are seen in their binding pockets. The pocket of 5-HT1B is much broader than <scene name='71/716548/5-ht2b/1'>that of 5-HT2B</scene>, due to a 3 Å shift of the top of helix V. Perhaps this difference highlights a variation in serotonin affinity between the two families. It has the characteristic 7 alpha helices and the N-terminus sticks out into extracellular space. <ref name="one" />

Lysergic Acid Diethylamide, more commonly known as LSD, is a potent hallucinogen and is derived from ergotamine, an ergopeptine whose structural skeleton is contained in a diverse range of alkaloids. LSD acts as a non-selective 5-HT receptor agonist, meaning it can bind with equal affinity to two or more sub-types of receptors. LSD actively binds in the <scene name='71/716548/5-ht2b/2'>orthosteric binding pocket</scene> to both the 5-HT1B and 5HT-2B receptors, suggesting a similar chemical structure and function between the two receptor families. The docking is stabilized by hydrogen bonding between the amino group of the 5-membered ring of LSD and the threonine residue of the 5-HT1B receptor, in a similar fashion that 5-HT would bind to said receptor. <ref name = "one" />