Molecular determinants of binding of a wasp toxin (PMTXs) and its analogs in the Na+ channels proteins.
The structural specificity of alpha-PMTX, a novel peptide toxin derived from wasp venom has been studied on the neuromuscular synapse in the walking leg of the lobster. alpha-PMTX is known to induce repetitive action potentials in the presynaptic axon due to sodium channel inactivation. We synthesized 29 analogs of alpha-PMTX by substituting one or two amino acids and compared threshold concentrations of these mutant toxins for inducing repetitive action potentials. In 13 amino acid residues of alpha-PMTX, Arg-1, Lys-3 and Lys-12 regulate the toxic activity because substitution of these basic amino acid residues with other amino acid residues greatly changed the potency. Determining the structure-activity relationships of PMTXs will help clarifying the molecular mechanism of sodium channel inactivation.
Konno
K
K
Institute of Biosciences at Rio Claro, São Paulo State University, Brazil.
Hisada
M
M
Naoki
H
H
Itagaki
Y
Y
Yasuhara
T
T
Nakata
Y
Y
Miwa
A
A
Kawai
N
N
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D019476:Insect Proteins; D008121:Nephropidae; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding; D015222:Sodium Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014862:Wasp Venoms / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
D019476:Insect Proteins; D009498:Neurotoxins; D015222:Sodium Channels; D014862:Wasp Venoms; C115328:pompilidotoxin alpha; C115329:pompilidotoxin beta