title: The synergic modeling for the binding of fluoroquinolone antibiotics to the hERG potassium channel.
abstract: 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.
authors.affiliation: CMC Center, Takeda Pharmaceutical Company Limited, Osaka 532-8686, Japan.
authors.forename: Sunghi
authors.initials: S
authors.lastname: Ryu
authors.forename: Yumi N
authors.initials: YN
authors.lastname: Imai
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Oiki
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D024841:Fluoroquinolones; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers