2m01
Solution structure of Kunitz-type neurotoxin LmKKT-1a from scorpion venom
Structural highlights
FunctionVKT21_LYCMC Dual-function toxin that completely inhibits trypsin activity at a molar ratio of 1:1 (Ki=140 nM) and that inhibits mKv1.3/KCNA3 potassium channel currents (1 uM inhibits 50% of currents) (IC(50)=1.58 uM). Shows also weak inhibition on Kv1.1/KCNA1 (1 uM inhibits 25% of currents) and Kv1.2/KCNA2 (1 uM inhibits 25% of currents).[1] [2] Publication Abstract from PubMedBACKGROUND: 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. Genomic and structural characterization of Kunitz-type peptide LmKTT-1a highlights diversity and evolution of scorpion potassium channel toxins.,Chen Z, Luo F, Feng J, Yang W, Zeng D, Zhao R, Cao Z, Liu M, Li W, Jiang L, Wu Y PLoS One. 2013;8(4):e60201. doi: 10.1371/journal.pone.0060201. Epub 2013 Apr 3. PMID:23573241[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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