Insight into the Mode of Action of 8-Hydroxyquinoline-Based Blockers on the Histamine Receptor 2.

ABSTRACT: Histamine receptor 2 (HR_H2) blockers are used to treat peptic ulcers and gastric reflux. Chlorquinaldol and chloroxine, which contain an 8-hydroxyquinoline (8HQ) core, have recently been identified as blocking HR_H2. To gain insight into the mode of action of 8HQ-based blockers, here, we leverage an HR_H2-based sensor in yeast to evaluate the role of key residues in the HR_H2 active site on histamine and 8HQ-based blocker binding. We find that the HR_H2 mutations D98A, F254A, Y182A, and Y250A render the receptor inactive in the presence of histamine, while HR_H2:D186A and HR_H2:T190A retain residual activity. Based on molecular docking studies, this outcome correlates with the ability of the pharmacologically relevant h

SUBMITTER: Patel A 

PROVIDER: S-EPMC10295836 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature