1LQH

INSECTICIDAL ALPHA SCORPION TOXIN ISOLATED FROM THE VENOM OF SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, MINIMIZED AVERAGE STRUCTURE

Summary for 1LQH

• Entry DOI: 10.2210/pdb1lqh/pdb
• Descriptor: INSECT TOXIN ALPHA (1 entity in total)
• Functional Keywords: neurotoxin, sodium channel inhibitor
• Biological source: Leiurus quinquestriatus hebraeus
• Cellular location: Secreted: P17728
• Total number of polymer chains: 1
• Total formula weight: 7396.45

Authors

Tugarinov, V.,Kustanovich, I.,Zilberberg, N.,Gurevitz, M.,Anglister, J. (deposition date: 1996-06-17, release date: 1997-03-12, Last modification date: 2024-10-23)

Primary citation

Tugarinov, V.,Kustanovich, I.,Zilberberg, N.,Gurevitz, M.,Anglister, J.
Solution structures of a highly insecticidal recombinant scorpion alpha-toxin and a mutant with increased activity.
Biochemistry, 36:2414-2424, 1997

PubMed Abstract: The solution structure of a recombinant active alpha-neurotoxin from Leiurus quinquestriatus hebraeus, Lqh(alpha)IT, was determined by proton two-dimensional nuclear magnetic resonance spectroscopy (2D NMR). This toxin is the most insecticidal among scorpion alpha-neurotoxins and, therefore, serves as a model for clarifying the structural basis for their biological activity and selective toxicity. A set of 29 structures was generated without constraint violations exceeding 0.4 A. These structures had root mean square deviations of 0.49 and 1.00 A with respect to the average structure for backbone atoms and all heavy atoms, respectively. Similarly to other scorpion toxins, the structure of Lqh(alpha)IT consists of an alpha-helix, a three-strand antiparallel beta-sheet, three type I tight turns, a five-residue turn, and a hydrophobic patch that includes tyrosine and tryptophan rings in a "herringbone" arrangement. Positive phi angles were found for Ala50 and Asn11, suggesting their proximity to functionally important regions of the molecule. The sample exhibited conformational heterogeneity over a wide range of experimental conditions, and two conformations were observed for the majority of protein residues. The ratio between these conformations was temperature-dependent, and the rate of their interconversions was estimated to be on the order of 1-5 s(-1) at 308 K. The conformation of the polypeptide backbone of Lqh(alpha)IT is very similar to that of the most active antimammalian scorpion alpha-toxin, AaHII, from Androctonus australis Hector (60% amino acid sequence homology). Yet, several important differences were observed at the 5-residue turn comprising residues Lys8-Cys12, the C-terminal segment, and the mutual disposition of these two regions. 2D NMR studies of the R64H mutant, which is 3 times more toxic than the unmodified Lqh(alpha)IT, demonstrated the importance of the spatial orientation of the last residue side chain for toxicity of Lqh(alpha)IT.

PubMed: 9054546
DOI: 10.1021/bi961497l

Experimental method

SOLUTION NMR