703DSS
From Proteopedia
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== Structure == | == Structure == | ||
| - | The 5-HT3 receptor is bullet-shaped and consists of five subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the five subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of three regions; the extracellular region, the transmembrane region, and the intracellular region.<ref>Barnes, N., Hales, T., Lummis, S., & Peters, J. (2009). The 5-HT3 receptor – the relationship between structure and function. Neuropharmacology, 273-284</ref> | + | The 5-HT3 receptor is bullet-shaped and consists of five subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the five subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of three regions; the extracellular region, the transmembrane region, and the intracellular region.<ref name="barnes">Barnes, N., Hales, T., Lummis, S., & Peters, J. (2009). The 5-HT3 receptor – the relationship between structure and function. Neuropharmacology, 273-284</ref> |
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These <scene name='71/716487/Binding_site/1'>binding sites</scene> are located between two bordering subunits, assembled from three alpha-helices of one subunit and three beta-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing away from the binding pocket. <ref name="hassaine">Hassaine, G., Deluz, C., Grasso, L., Wyss, R., Tol, M., Hovius, R., . . . Nury, H. (2014). X-ray structure of the mouse serotonin 5-HT3 receptor. Nature, 276-281.</ref> This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them. | These <scene name='71/716487/Binding_site/1'>binding sites</scene> are located between two bordering subunits, assembled from three alpha-helices of one subunit and three beta-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing away from the binding pocket. <ref name="hassaine">Hassaine, G., Deluz, C., Grasso, L., Wyss, R., Tol, M., Hovius, R., . . . Nury, H. (2014). X-ray structure of the mouse serotonin 5-HT3 receptor. Nature, 276-281.</ref> This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them. | ||
| - | The transmembrane region is within the C-terminus region, and contains four alpha-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These four alpha-helical domains conduct the channel openings via ion selectivity, depending on both charge and size.<ref name="hassaine" /> M2, the porous domain, contains rings of charged amino acids at both its start and its end, accounting for M2’s main contribution to ion selectivity. The M3 and M4 alpha-helices create a large loop with one another, thus assembling the intracellular region | + | The transmembrane region is within the C-terminus region, and contains four alpha-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These four alpha-helical domains conduct the channel openings via ion selectivity, depending on both charge and size.<ref name="hassaine" /> M2, the porous domain, contains rings of charged amino acids at both its start and its end, accounting for M2’s main contribution to ion selectivity. The M3 and M4 alpha-helices create a large loop with one another, thus assembling the intracellular region. <ref name="barnes"> |
== Function == | == Function == | ||
Revision as of 01:22, 7 December 2015
5-HT3a Receptor
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References
- ↑ 1.0 1.1 Barnes, N., Hales, T., Lummis, S., & Peters, J. (2009). The 5-HT3 receptor – the relationship between structure and function. Neuropharmacology, 273-284
- ↑ Perumal, R., & Mahesh, R. (2006). Synthesis and biological evaluation of a novel structural type of serotonin 5-HT3 receptor antagonists. Bioorganic & Medicinal Chemistry Letters, 2769-2772.
- ↑ 3.0 3.1 Hassaine, G., Deluz, C., Grasso, L., Wyss, R., Tol, M., Hovius, R., . . . Nury, H. (2014). X-ray structure of the mouse serotonin 5-HT3 receptor. Nature, 276-281.
Galligan, J. J. (2002). Ligand-gated ion channels in the enteric nervous system. Neurogastroenterology & Motility, 14(6), 611-623. doi: 10.1046/j.1365-2982.2002.00363.x
Glennon, Richard A., Malgorzata Dukat, and Richard B. Westkaemper. (2000). Serotonin receptor subtypes and ligands. American College of Neuropsychopharmacology.
Gupta, D., Thangaraj, D., & Radhakrishnan, M. (2016). A novel 5HT3 antagonist 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide) prevents diabetes-induced depressive phenotypes in mice: Modulation of serotonergic system. Behavioural Brain Research, 297, 41-50. doi:10.1016/j.bbr.2015.10.007
Hannon, J., & Hoyer, D. (2008). Research report: molecular biology of 5-HT receptors. Behavioural Brain Research, 195(Serotonin and cognition: mechanisms and applications), 198-213. doi:10.1016/j.bbr.2008.03.020
Kurhe, Y. V., Radhakrishnan, M., Thangaraj, D., & Gupta, D. (2014). Anti-anxiety effect of a novel 5-HT3 receptor antagonistN-(benzo[d]thiazol-2-yl)-3-ethoxyquinoxalin-2- carboxamide (6k) using battery tests for anxiety in mice. Indian Journal of Pharmacology, 46(1), 100–104. doi: 10.4103/0253-7613.125186
Morrison, T. R., Ricci, L. A., & Melloni, R. H., Jr. (2015). Aggression and anxiety in adolescent AAS-treated hamsters: A role for 5HT3 receptors. Pharmacology Biochemistry and Behavior, 134, 85-91. doi:10.1016/j.pbb.2015.05.001
Serotonin - Receptors and effects. (n.d.). Retrieved November 14, 2015, from http://www.pharmacorama.com/en/Sections/Serotonin_2_2.php
Thompson, A. J., & Lummis, S. C. R. (2006). 5-HT3 receptors. Current Pharmaceutical Design, 12(28), 3615–3630.
Barnes, N., Hales, T., Lummis, S., & Peters, J. (2009). The 5-HT3 receptor – the relationship between structure and function. Neuropharmacology, 273-284.
Hassaine, G., Deluz, C., Grasso, L., Wyss, R., Tol, M., Hovius, R., . . . Nury, H. (2014). X-ray structure of the mouse serotonin 5-HT3 receptor. Nature, 276-281.
Perumal, R., & Mahesh, R. (2006). Synthesis and biological evaluation of a novel structural type of serotonin 5-HT3 receptor antagonists. Bioorganic & Medicinal Chemistry Letters, 2769-2772.
