title: Molecular dynamics of the honey bee toxin tertiapin binding to Kir3.2.
abstract: Tertiapin (TPN), a short peptide isolated from the venom of the honey bee, is a potent and selective blocker of the inward rectifier K+(Kir) channel Kir3.2. Here we examine in atomic detail the binding mode of TPN to Kir3.2 using molecular dynamics, and deduce the key residue in Kir3.2 responsible for TPN selectivity. The binding of TPN to Kir3.2 is stable when the side chain of either Lys16 (TPNK16-Kir3.2) or Lys17 (TPNK17-Kir3.2) of the toxin protrudes into the channel pore. However, the binding affinity calculated from only TPNK17-Kir3.2 and not TPNK16-Kir3.2 is consistent with experiment, suggesting that Lys17 is the most plausible pore-blocking residue. The alanine mutation of Kir3.2-Glu127, which is not present in TPN-resistant channels, reduces the inhibitory ability of TPN by over 50 fold in TPNK17-Kir3.2, indicating that Kir3.2-Glu127 is important for the selectivity of TPN.
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Daxu
authors.initials: D
authors.lastname: Li
authors.affiliation: Research School of Biology, Australian National University, Acton, ACT 2601, Australia. Electronic address: rong.chen@anu.edu.au.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Research School of Biology, Australian National University, Acton, ACT 2601, Australia.
authors.forename: Shin-Ho
authors.initials: SH
authors.lastname: Chung
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000737:chemistry* / Q000378:metabolism; D001516:Bees; D001665:Binding Sites; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D001514:Bee Venoms; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D010713:Phosphatidylcholines; C029738:tertiapin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Honey bee toxin; Kir3.2; Molecular dynamics; Tertiapin