title: New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.
abstract: The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia. july@ibch.ru
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Korolkova
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.forename: Kamilla
authors.initials: K
authors.lastname: Angelo
authors.forename: Innokenty V
authors.initials: IV
authors.lastname: Maslennikov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Grinenko
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Lipkin
authors.forename: Elena D
authors.initials: ED
authors.lastname: Nosyreva
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Pluzhnikov
authors.forename: Soren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010957:Plasmids; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000633:toxicity; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013379:Substrate Specificity; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: C425305:BeKm-1 toxin; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D012996:Solutions; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG