PDBsum entry: 1seg

Toxin

PDB id: 1seg

Contents

Protein chain

64 a.a. *

Ligands

SO4

NO3 ×2

PPI

Waters ×119

* Residue conservation analysis

PDB id:

1seg

Name:

Toxin

Title:

Crystal structure of a toxin chimera between lqh-alpha-it from the scorpion leiurus quinquestriatus hebraeus and aah2 from androctonus australis hector

Structure:

Aah2: lqh-alpha-it (face) chimeric toxin. Chain: a. Synonym: aah ii, aahii, aah2. Engineered: yes. Mutation: yes

Source:

Androctonus australis hector. Organism_taxid: 70175. Strain: hector. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

1.30Å R-factor: 0.155 R-free: 0.178

Authors:

I.Karbat,F.Frolow,O.Froy,N.Gilles,L.Cohen,M.Turkov,D.Gordon, M.Gurevitz

Key ref:

I.Karbat et al. (2004). Molecular basis of the high insecticidal potency of scorpion alpha-toxins. J Biol Chem, 279, 31679-31686. PubMed id: 15133045 DOI: 10.1074/jbc.M402048200

Date:

17-Feb-04 Release date: 31-Aug-04

Protein chain

P01484  (SCX2_ANDAU) -  Alpha-mammal toxin AaH2

Seq: 85 a.a.

Struc: 64 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: defense response (1 term)
• Biochemical function: ion channel inhibitor activity (1 term)

DOI no: 10.1074/jbc.M402048200

J Biol Chem 279:31679-31686 (2004)

PubMed id: 15133045

Molecular basis of the high insecticidal potency of scorpion alpha-toxins.

I.Karbat, F.Frolow, O.Froy, N.Gilles, L.Cohen, M.Turkov, D.Gordon, M.Gurevitz.

ABSTRACT

Scorpion alpha-toxins are similar in their mode of action and three-dimensional structure but differ considerably in affinity for various voltage-gated sodium channels (NaChs). To clarify the molecular basis of the high potency of the alpha-toxin LqhalphaIT (from Leiurus quinquestriatus hebraeus) for insect NaChs, we identified by mutagenesis the key residues important for activity. We have found that the functional surface is composed of two distinct domains: a conserved "Core-domain" formed by residues of the loops connecting the secondary structure elements of the molecule core and a variable "NC-domain" formed by a five-residue turn (residues 8-12) and a C-terminal segment (residues 56-64). We further analyzed the role of these domains in toxin activity on insects by their stepwise construction onto the scaffold of the anti-mammalian alpha-toxin, Aah2 (from Androctonus australis hector). The chimera harboring both domains, Aah2(LqhalphaIT(face)), was as active to insects as LqhalphaIT. Structure determination of Aah2(LqhalphaIT(face)) by x-ray crystallography revealed that the NC-domain deviates from that of Aah2 and forms an extended protrusion off the molecule core as appears in LqhalphaIT. Notably, such a protrusion is observed in all alpha-toxins active on insects. Altogether, the division of the functional surface into two domains and the unique configuration of the NC-domain illuminate the molecular basis of alpha-toxin specificity for insects and suggest a putative binding mechanism to insect NaChs.

Selected figure(s)

Figure 2.
FIG. 2. CD spectra of recombinant Lqh IT and representative derivatives with altered or unchanged spectra.

Figure 6.
FIG. 6. The binding pocket of Arg-58. A, interaction with the sulfate ion that co-crystallized with the chimeric toxin. B, putative interaction with a Glu residue of the receptor binding site (dashed yellow lines) modeled according to the coordinates of the sulfate ion.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 31679-31686) copyright 2004.

Figures were selected by an automated process.