Histamine complex dating
Under physiological conditions, the aliphatic amino group (having a p K Thus, histamine is normally protonated to a singly charged cation. Histamine is derived from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. Once formed, histamine is either stored or rapidly inactivated by its primary degradative enzymes, histamine-N-methyltransferase or diamine oxidase.In the central nervous system, histamine released into the synapses is primarily broken down by histamine-N-methyltransferase, while in other tissues both enzymes may play a role.This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of HThis work was supported by the ERATO Human Receptor Crystallography Project from the Japan Science and Technology Agency and by the Targeted Proteins Research Program of MEXT (S. designed, characterized and screened the constructs, purified the receptor, and prepared the manuscript. collected the data and processed diffraction data with G. Analysis of drugprotein interactions should facilitate the development of antihistamines that are more selective and less likely to cause side effects than those currently available.
Wu for help with the preparation of Supplementary Fig. Xu for help on validation of data processing and A. , 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. refined the structure and assisted with preparing the manuscript. designed the receptor production strategy and assisted with preparing the manuscript.