2M01: Solution structure of Kunitz-type neurotoxin LmKKT-1a from scorpion venom

BACKGROUND: Recently, a new subfamily of long-chain toxins with a Kunitz-type fold was found in scorpion venom glands. Functionally, these toxins inhibit protease activity and block potassium channels. However, the genomic organization and three-dimensional (3-D) structure of this kind of scorpion toxin has not been reported. PRINCIPAL FINDINGS: Here, we characterized the genomic organization and 3-D nuclear magnetic resonance structure of the scorpion Kunitz-type toxin, LmKTT-1a, which has a unique cysteine pattern. The LmKTT-1a gene contained three exons, which were interrupted by two introns located in the mature peptide region. Despite little similarity to other Kunitz-type toxins and a unique pattern of disulfide bridges, LmKTT-1a possessed a conserved Kunitz-type structural fold with one alpha-helix and two beta-sheets. Comparison of the genomic organization, 3-D structure, and functional data of known toxins from the alpha-KTx, beta-KTx, gamma-KTx, and kappa-KTx subfamily suggested that scorpion Kunitz-type potassium channel toxins might have evolved from a new ancestor that is completely different from the common ancestor of scorpion toxins with a CSalpha/beta fold. Thus, these analyses provide evidence of a new scorpion potassium channel toxin subfamily, which we have named delta-KTx. CONCLUSIONS/SIGNIFICANCE: Our results highlight the genomic, structural, and evolutionary diversity of scorpion potassium channel toxins. These findings may accelerate the design and development of diagnostic and therapeutic peptide agents for human potassium channelopathies.
PDB ID: 2M01Download
MMDB ID: 114983
PDB Deposition Date: 2012/10/15
Updated in MMDB: 2013/11
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2M01: monomeric; determined by author
Molecular Components in 2M01
Label Count Molecule
Protein (1 molecule)
Protease Inhibitor Lmktt-1a
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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