TY - JOUR
T1 - New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1
AU - Korolkova, Yuliya V.
AU - Bocharov, Eduard V.
AU - Angelo, Kamilla
AU - Maslennikov, Innokenty V.
AU - Grinenko, Olga V.
AU - Lipkin, Aleksey V.
AU - Nosyreva, Elena D.
AU - Pluzhnikov, Kirill A.
AU - Olesen, Søren Peter
AU - Arseniev, Alexander S.
AU - Grishin, Eugene V.
PY - 2002/11/8
Y1 - 2002/11/8
N2 - 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 α-helix and a triple-stranded antiparallel β-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 α-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the β-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.
AB - 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 α-helix and a triple-stranded antiparallel β-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 α-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the β-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.
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U2 - 10.1074/jbc.M204083200
DO - 10.1074/jbc.M204083200
M3 - Article
C2 - 12151390
AN - SCOPUS:0037044745
SN - 0021-9258
VL - 277
SP - 43104
EP - 43109
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -