The study identifies specific amino acid residues in the hERG potassium channel responsible for binding and blockade by fluoroquinolone antibiotics, providing mechanistic insight into their proarrhythmic potential.
May inform fluoroquinolone cardiotoxicity models; hypothesis-generating for hERG-targeted arrhythmia research.
The fluoroquinolone antibiotic binding site in the hERG potassium channel was examined for the residues involved and their position in the tetrameric channel. The blocking effect of the two fluoroquinolones levofloxacin and sparfloxacin to tandem dimers of the hERG mutants were evaluated electrophysiologically. The results indicated that two Tyr652s in the neighboring subunits and one or two Phe656s in the diagonal subunits contributed to the blockade in the case of both compounds, and Ser624 was also involved. The docking studies suggested that the protonated carboxyl group in the compounds strongly interacts with Phe656 as a π acceptor.
No takes yet. Share an insight, caveat, or question.
Ryu et al. (2013) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: