Histamine H1 receptor: Difference between revisions
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The structure of the H1 histamine receptor bound to an antihistamine, doxepin was published in 2011 <ref>PMID:21697825</ref>. A <scene name='78/784820/N_to_c_rainbow/1'>N-->C rainbow</scene> view colors the N terminus blue and the C terminus red, with the intervening segments paralleling the rainbow (blue, green, yellow, orange, red). This image is oriented with the transmembrane section at the top and the cytosolic portion below. The <scene name='78/784820/Hydrophobic/2'>hydrophobic residues</scene> are shown in grey, while hydrophilic amino acids are shown in purple. | The structure of the H1 histamine receptor bound to an antihistamine, doxepin was published in 2011 <ref>PMID:21697825</ref>. A <scene name='78/784820/N_to_c_rainbow/1'>N-->C rainbow</scene> view colors the N terminus blue and the C terminus red, with the intervening segments paralleling the rainbow (blue, green, yellow, orange, red). This image is oriented with the transmembrane section at the top and the cytosolic portion below. The <scene name='78/784820/Hydrophobic/2'>hydrophobic residues</scene> are shown in grey, while hydrophilic amino acids are shown in purple. | ||
<scene name='78/784820/Doxepin/3'>Doxepin</scene> binds among the transmembrane alpha helices. Binding is stabilized by a number of <scene name='78/784820/Interacting_amino_acids/4'>interactions with amino acids</scene>. Like many G protein coupled receptors, the bottom of the binding pocket contains a conserved <scene name='78/784820/Trp_428/1'>tryptophan</scene> residue. Interestingly, second generation antihistamines take advantage of an anion binding site formed by <scene name='78/784820/Lys/2'>two lysine residues</scene>; in this structure, they interact with a phosphate. | <scene name='78/784820/Doxepin/3'>Doxepin</scene> was originally made as a tricyclic antidepressant, but it also is a potent antihistamine <ref>PMID: 39202</ref> binds among the transmembrane alpha helices. Binding is stabilized by a number of <scene name='78/784820/Interacting_amino_acids/4'>interactions with amino acids</scene>. Like many G protein coupled receptors, the bottom of the binding pocket contains a conserved <scene name='78/784820/Trp_428/1'>tryptophan</scene> residue. Interestingly, second generation antihistamines take advantage of an anion binding site formed by <scene name='78/784820/Lys/2'>two lysine residues</scene>; in this structure, they interact with a phosphate. | ||
Like other [[G protein-coupled receptor]]s, the Histamine H1 Receptor contains a <scene name='78/784820/Dry_motif/1'>conserved DRY</scene> (aspartate (D), arginine (R), tyrosine (Y)) motif in the seven helix transmembrane surface near the cytosolic face. In some G protein receptors, an "ionic lock" interaction between the asparate and arginine in this motif stabilizes the inactive state<ref>PMID:17192495</ref>; however, in the Histamine H1 receptor, Arginine 125 forms a hydrogen bond with <scene name='78/784820/Arg125_gln_416_salt_bridge/1'>glutamine 416</scene>, which stabilizes the inactive state. | Like other [[G protein-coupled receptor]]s, the Histamine H1 Receptor contains a <scene name='78/784820/Dry_motif/1'>conserved DRY</scene> (aspartate (D), arginine (R), tyrosine (Y)) motif in the seven helix transmembrane surface near the cytosolic face. In some G protein receptors, an "ionic lock" interaction between the asparate and arginine in this motif stabilizes the inactive state<ref>PMID:17192495</ref>; however, in the Histamine H1 receptor, Arginine 125 forms a hydrogen bond with <scene name='78/784820/Arg125_gln_416_salt_bridge/1'>glutamine 416</scene>, which stabilizes the inactive state. | ||