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001-es BibID:	BIBFORM004689
Első szerző:	Péter Mózes (orvos, neuroradiológus) ifj.
Cím:	Effects of toxins Pi2 and Pi3 on human T lymphocyte Kv1.3 channels : the role of Glu7 and Lys24 / Peter, M., Jr., Varga, Z., Hajdu, P., Gaspar, R., Damjanovich, S., Horjales, E., Possani, L. D., Panyi, G.
Dátum:	2001
Megjegyzések:	Pandinus imperator scorpion toxins Pi2 and Pi3 differ only by a single amino acid residue (neutral Pro7 in Pi2 vs. acidic Glu7 in Pi3). The binding kinetics of these toxins to human Kv1.3 showed that the decreased ON rate (k(ON) = 2.18 x 10(8) m(-1)sec(-1) for Pi2 and 1.28 x 10(7) m(-1)sec(-1) for Pi3) was almost entirely responsible for the increased dissociation constant (K(d)) of Pi3 (K(d) = 795 pm) as compared to Pi2 (K(d) = 44 pm). The ionic strength dependence of the association rates was exactly the same for the two toxins indicating that through-space electrostatic interactions can not account for the different ON rates. Results were further analyzed on the basis of the three-dimensional structural models of the toxins. A 3D structure of Pi3 was generated from the NMR spectroscopy coordinates of Pi2 by computer modeling. The Pi3 model resulted in a salt bridge between Glu7 and Lys24 in Pi3. Based on this finding our interpretation of the reduced ON rate of Pi3 is that the intramolecular salt bridge reduces the local positive electrostatic potential around Lys24 resulting in decreased short-range electrostatic interactions during the binding step. To support our finding, we constructed a 3D model of the Ser-10-Asp Charybdotoxin mutant displaying distinctly reduced affinity for Shaker channels. The mutant Charybdotoxin structure also displayed a salt bridge between residues Asp10 and Lys27 equivalent to the one between Glu7 and Lys24 in Pi3.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Amino Acid Sequence Animal Charybdotoxin chemistry drug effects genetics Glutamic Acid Human Hungary In Vitro Kinetics Lysine Membrane Potentials metabolism Models,Molecular Molecular Sequence Data pharmacology Point Mutation Potassium Potassium Channel Blockers Potassium Channels Protein Conformation Scorpion Venoms Sequence Homology,Amino Acid Support,Non-U.S.Gov't T-Lymphocytes Toxins
Megjelenés:	The Journal of Membrane Biology. - 179 : 1 (2001), p. 13-25. -
További szerzők:	Varga Zoltán (1969-) (biofizikus, szakfordító) Hajdu Péter (1975-) (biofizikus) Gáspár Rezső (1944-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus) Horjales, E. Possani, Lourival Domingos Panyi György (1966-) (biofizikus)
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001-es BibID:	BIBFORM004670
Első szerző:	Péter Mózes (orvos, neuroradiológus) ifj.
Cím:	Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin / Peter, M., Jr., Hajdu, P., Varga, Z., Damjanovich, S., Possani, L. D., Panyi, G., Gaspar, R.
Dátum:	2000
Megjegyzések:	Using the patch-clamp technique we determined that Pandinus imperator toxin Pi1, a recently described peptide toxin having four disulfide bridges instead of the usual three in scorpion toxins, blocked Kv1.3 channels of human T lymphocytes from the extracellular side with a 1:1 stoichiometry. Kv1.3 block was instantaneous and removable with toxin-free extracellular solution. The toxin did not influence activation or inactivation of the channels. We found that Pi1 blocked Kv1.3 with less affinity (K(d) = 11.4 nM) than the structurally related three disulfide bridge containing toxins Pi2 (50 pM) and Pi3 (0.5 nM). The fourth disulfide bridge in Pi1 had no influence on the channel binding ability of the toxin; the less effective block was due to differences in amino acid side chain properties at positions 11 and 35.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Amino Acid Sequence Amino Acids Animal chemistry Disulfides drug effects Human Hungary Kinetics Lymphocytes metabolism Molecular Sequence Data Patch-Clamp Techniques pharmacology Potassium Potassium Channels Protein Binding Scorpion Venoms Scorpions Sequence Homology,Amino Acid Support,Non-U.S.Gov't T-Lymphocytes Time Factors Toxins
Megjelenés:	Biochemical and Biophysical Research Communications. - 278 : 1 (2000), p. 34-37. -
További szerzők:	Hajdu Péter (1975-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Damjanovich Sándor (1936-2017) (biofizikus) Possani, Lourival Domingos Panyi György (1966-) (biofizikus) Gáspár Rezső (1944-) (biofizikus)
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