title: Binding pathway of histamine to the hH4R, observed by unconstrained molecular dynamics.
abstract: Histamine binds with high affinity to the human histamine H4 receptor (hH4R). We are the first to examine the complete binding pathway of histamine from the extracellular side to the orthosteric binding site of the hH4R by means of unconstrained molecular dynamic simulation. Furthermore, the simulations show that the positively charged amine moiety of the histamine interacts electrostatically with the highly conserved Asp(3.32), while the imidazole moiety forms a hydrogen bond interaction with Glu(5.46) and Gln(7.42).
authors: Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, D-93040 Regensburg, Germany.
authors: Hans-Joachim
authors: HJ
authors: Wittmann
authors: Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, D-93040 Regensburg, Germany. Electronic address: andrea.strasser@chemie.uni-regensburg.de.
authors: Andrea
authors: A
authors: Strasser
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D011968:Receptors, Histamine / Q000737:chemistry* / Q000378:metabolism; D000074040:Receptors, Histamine H4; D016415:Sequence Alignment; D055672:Static Electricity
chemical_list: C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
keywords: Histamine; Histamine H(4) receptor; Ligand binding pathway; Molecular dynamics