Download Structure and Function of a Human Histamine Receptor Elena A

Structure and Function of a Human Histamine Receptor
Elena A. Fabrikant, Nagarajan Vaidehi, William A. Goddard III.
The Histamine H2 Receptor (HRH2) belongs to a family of G – protein coupled
receptors that are responsible for binding histamine, a biogenic amine which is known to
be directly involved in the physiological effects of anaphylaxis. HRH2 itself has been
shown to regulate smooth and cardiac muscle relaxation, induction of suppressor T cells,
granulocyte differentiation, and intestinal secretions. Histamine receptors have long been
utilized as pharmacological targets for treatment of anaphylaxis and acid peptic disorders.
A number of agonists and antagonists have already been successfully developed in the
clinical setting. Furthermore, several of the HRH2 antagonists have been shown to
exhibit 'inverse agonist' behavior, reducing the activity of the receptor below basal levels. The structure of the HRH2 receptor is predicted from first principles using the
Membstruk protocol, and the resulting predictions are validated by comparison with
experimental mutagenesis studies. These results will be used to model the binding of
known and novel HRH2 pharmacological targets using the HierDock procedure, and it is
hoped that the model will shed new light on the differences between agonist, antagonist,
and inverse agonist binding.