@article {Zhang:2012:1573-4064:1084,
title = "Homology Modeling and Antagonist Binding Site Study of the Human Histamine H2 Receptor",
journal = "Medicinal Chemistry",
parent_itemid = "infobike://ben/mc",
publishercode ="ben",
year = "2012",
volume = "8",
number = "6",
publication date ="2012-11-01T00:00:00",
pages = "1084-1092",
itemtype = "ARTICLE",
issn = "1573-4064",
url = "https://www.ingentaconnect.com/content/ben/mc/2012/00000008/00000006/art00012",
doi = "doi:10.2174/157340612804075223",
keyword = "Human histamine H2 receptor, Homology modeling, Molecular
dynamics, Binding site, Molecular docking, Antagonists",
author = "Zhang, Jing and Qi, Tao and Wei, Jing",
abstract = "On the basis of the high resolution crystal structures of bovine rhodopsin, human beta2-adrenergic receptor and human A2a adenosine receptor, three-dimensional structure of the human histamine H2 receptor (HHR2) was developed by homology modeling. Results of the evaluations suggest
that a high quality homology model for HHR2 has been obtained. Three antagonists, cimetidine, ranitidine and nizatidine, were applied to binding site study with this model through molecular docking, molecular dynamics simulations and the molecular mechanics-Poisson-Boltzmann surface area calculations.
One aspartic acid, Asp98 in transmembrane domain 7 (TM3), has been identified as major contributors to ligand binding by H-bond interactions. Asn159 in TM4 and Asp186 in TM5 are of great importance in stabilizing HHR2- antagonist complexes. Two hydrophobic sites especially two residues, Val99
in TM3 and Phe254 in TM6, were identified to be essential for their strong hydrophobic interactions with antagonists. The findings reported here are in agreement with available experimental mutagenesis data. This study should be very helpful for a better understanding of the action mode of
the antagonist and for guiding further drug design and mutagenesis studies.",
}