User:Snehalatha Kaliappan/Histamine
From Proteopedia
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Structure of Histamine
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Histamine is an organic compound containing nitrogen atoms found in some of the human body cells. It is part of the immune system that causes the allergy related symptoms such as itching, sneezing and cold like symptoms. It also acts like a neurotransmitter in brain, spinal cord and uterus. It also regulates physiological functions in gut. The imidazole ring of the histamine can have two tautomeric forms depending on which of the two nitrogens' is protonated. The nitrogen farther away from the side chain is the 'tele' nitrogen and is denoted by a lowercase tau sign and the nitrogen closer to the side chain is the 'pros' nitrogen and is denoted by the pi sign. The tele tautomer, Nτ-H-histamine, is preferred in solution as compared to the pros tautomer, Nπ-H-histamine.
References
https://en.wikipedia.org/wiki/Histamine https://www.sciencedirect.com/science/article/pii/S0166128003006523 https://www.researchgate.net/publication/235351330_Microsolvation_of_the_histamine_monocation_in_aqueous_solution_The_effect_on_structure_hydrogen_bonding_ability_and_vibrational_spectrum#pf2
Histamine H1 Receptor
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Histamine receptors belong to class A of the GPCR superfamily(G protein‐coupled receptors) contain a bundle of seven antiparallel transmembrane helices. Histamine binds to these receptors as primary endogenous ligand. There are 4 known histamine receptors, H1, H2, H3 and H4. H1 receptor is expressed in It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system.The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs.The crystal structure of the histamine H 1 receptor was obtained in 2011 and is still the only structureof histaminergic receptor deposited in the Protein Data Bank( PDB ID: 3RZE). It shows the crystal structure of the H1 receptor complex with doxepin, a first-generation H1 receptor antagonist.Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 428, a highly conserved key residue in G-protein-coupled-receptor activation.This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys 191(5.39) and/or Lys 179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules.
References
Structure of the human histamine H1 receptor complex with doxepin. Nature 2011, 475, 65–70. doi:10.1038/nature10236
https://www.sciencedirect.com/topics/medicine-and-dentistry/histamine-h1-receptor
