Neurotoxin with binding properties to voltage-gated sodium channels

A Chain A, Nmr Structures Of Lqh Iii Alpha-Like Scorpion Toxin From Leiurus Quinquestriatus Corresponding To The Major Conformer In Solution

Alpha-Like Toxin Lqh Iii From Scorpion Leiurus Quinquestriatus Hebraeus, Nmr, 25 Structures

The chemical shifts listed concern the major conformer in solution

Information obtained from PDB's Chemical Component Dictionary at http://wwpdb-remediation.rutgers.edu/downloads.html Downloaded on Thu Jul 14 16:09:34 2011

A Cis-trans Isomerism of a Non-prolyl Peptide Bond in Lqh III Alpha-like Scorpion Toxin Revealed by Solution NMR

Pons, J.L., Malliavin, T.E. and Delsuc, M.A., 1996. Gifa V4 : a complete package for NMR data-set processing. J. Biomol. NMR, 8, 445-452.

NMR structures of a new toxin from the scorpion Leiurus quinquestriatus hebraeus (Lqh III) have been investigated in conjunction with its pharmacological properties. This toxin is proposed to belong to a new group of scorpion toxins, the alpha-like toxins that target voltage-gated sodium channels with specific properties compared with the classical alpha-scorpion toxins. Electrophysiological analysis showed that Lqh III inhibits a sodium current inactivation in the cockroach axon, but induces in addition a resting depolarization due to a slowly decaying tail current atypical to other alpha-toxin action. Binding studies indicated that radiolabeled Lqh III binds with a high degree of affinity (Ki=2.2 nM) on cockroach sodium channels and that the alpha-toxin from L quinquestriatus hebraeus highly active on insects (LqhalphaIT) and alpha-like toxins compete at low concentration for its receptor binding site, suggesting that the alpha-like toxin receptor site is partially overlapping with the receptor site 3. Conversely, in rat brain, Lqh III competes for binding of the most potent anti-mammal alpha-toxin from Androctonus australis Hector venom (AaH II) only at very high concentration.The NMR structures were used for the scrutiny of the similarities and differences with representative scorpion alpha-toxins targeting the voltage-gated sodium channels of either mammals or insects. Three turn regions involved in the functional binding site of the anti-insect LqhalphaIT toxin reveal significant differences in the Lqh III structure. The electrostatic charge distribution in the Lqh III toxin is also surprisingly different when compared with the anti-mammal alpha-toxin AaH II. Similarities in the electrostatic charge distribution are, however, recognized between alpha-toxins highly active on insects and the alpha-like toxin Lqh III. This affords additional important elements to the definition of the new alpha-like group of scorpion toxins and the mammal versus insect scorpion toxin selectivities.
Krimm, I. et al (1999) NMR Structures and Activity of a Novel Alpha-Like Toxin from the Scorpion Leiurus quinquestriatus hebraeus. J. Mol. Biol., 285: 1749-1763.
NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus quinquestriatus hebraeus.

The molecule is characterized by a mixture of cis (major form) and trans (minor form) Pro9-Glu10 peptide bond in slow exchange on the NMR chemical shift time scale.

Nmr Structures Of Lqh Iii Alpha-Like Scorpion Toxin From Leiurus Quinquestriatus Corresponding To The Major Conformer In Soluti

RecName: Full=Alpha-like toxin Lqh3; AltName: Full=Lqh III; Short=LqhIII [Leiurus quinquestriatus hebraeus]

1H Chemical Shift Assignment for the Major Conformer in Solution of the Alpha-like Scorpion Toxin LqhIII