TAILIEUCHUNG - Báo cáo Y học: A single charged surface residue modifies the activity of ikitoxin, a beta-type Na+ channel toxin from Parabuthus transvaalicus

We previously purified and characterized a peptide toxin, birtoxin, from the South African scorpion Parabuthus transvaalicus. Birtoxin is a 58-residue, long chain neurotoxin that has a unique three disulfide-bridged structure. Here we report the isolation and characterization of ikitoxin, a pep-tide toxin with a single residue difference, and a markedly reducedbiological activity, frombirtoxin. Bioassays onmice showed that high doses of ikitoxin induce unprovoked jumps, whereas birtoxin induces jumps at a 1000-fold lower concentration. . | Eur. J. Biochem. 269 5369-5376 2002 FEBS 2002 doi A single charged surface residue modifies the activity of ikitoxin a beta-type Na channel toxin from Parabuthus transvaalicus A. Bora inceoglu1 I Yuki Hayashida2 Jozsef Lango3 Andrew T. Ishida2 and Bruce D. Hammock1 1 Department of Entomology and Cancer Research Center 2Section of Neurobiology Physiology and Behavior and 3Department of Chemistry and Superfund Analytical Laboratory University of California Davis CA USA We previously purified and characterized a peptide toxin birtoxin from the South African scorpion Parabuthus transvaalicus. Birtoxin is a 58-residue long chain neurotoxin that has a unique three disulfide-bridged structure. Here we report the isolation and characterization of ikitoxin a peptide toxin with a single residue difference and a markedly reduced biological activity from birtoxin. Bioassays on mice showed that high doses of ikitoxin induce unprovoked jumps whereas birtoxin induces jumps at a 1000-fold lower concentration. Both toxins are active against mice when administered intracerebroventricularly. Mass determination indicated an apparent mass of 6615 Da for ikttoxin VS. 6543 Da for birtoxin. Amino acid sequence determination revealed that the amino-acid sequence of ikitoxin differs from birtoxin by a single residue change from glycine to glutamic acid at position 23 consistent with the apparent mass difference of 72 Da. This single-residue difference renders ikitoxin much less effective in producing the same behavioral effect as low concentrations of birtoxin. Electrophysiological measurements showed that birtoxin and ikitoxin can be classified as beta group toxins for voltagegated Na channels of central neurons. It is our conclusion that the N-terminal loop preceding the a-helix in scorpion toxins is one of the determinative domains in the interaction of toxins with the target ion channel. Keywords birtoxin ikitoxin Parabuthus scorpion voltagegated Na .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine