title: Structural basis of the KcsA K(+) channel and agitoxin2 pore-blocking toxin interaction by using the transferred cross-saturation method.
abstract: We have determined the binding site on agitoxin2 (AgTx2) to the KcsA K(+) channel by a transferred cross-saturation (TCS) experiment. The residues significantly affected in the TCS experiments formed a contiguous surface on AgTx2, and substitutions of the surface residues decreased the binding affinity to the KcsA K(+) channel. Based on properties of the AgTx2 binding site with the KcsA K(+) channel, we present a surface motif that is observed in pore-blocking toxins affecting the K(+) channel. Furthermore, we also explain the structural basis of the specificity of the K(+) channel to the toxins. The TCS method utilized here is applicable not only for the channels, which are complexed with other inhibitors, but also with a variety of regulatory molecules, and provides important information about their interface in solution.
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan.
authors: Koh
authors: K
authors: Takeuchi
authors: Mariko
authors: M
authors: Yokogawa
authors: Tomoki
authors: T
authors: Matsuda
authors: Mariko
authors: M
authors: Sugai
authors: Seiko
authors: S
authors: Kawano
authors: Toshiyuki
authors: T
authors: Kohno
authors: Haruki
authors: H
authors: Nakamura
authors: Hideo
authors: H
authors: Takahashi
authors: Ichio
authors: I
authors: Shimada
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004926:Escherichia coli / Q000378:metabolism; D005822:Genetic Vectors; D007477:Ions; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D007477:Ions; D015221:Potassium Channels; D012604:Scorpion Venoms; C107790:prokaryotic potassium channel; C087603:agitoxin 2; D011188:Potassium