Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2004 Mar 15;378Pt 3:745-52. doi: 10.1042/BJ20031324.
Show Gene links
Show Anatomy links
BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.
Huys I, Xu CQ, Wang CZ, Vacher H, Martin-Eauclaire MF, Chi CW, Tytgat J.
???displayArticle.abstract???
A novel HERG channel blocker was isolated from the venom of the scorpion Buthus martensi Karsch, sequenced and characterized at the pharmacological level after chemical synthesis. According to the determined amino acid sequence, the cDNA and genomic genes were then cloned. The genomic gene consists of two exons interrupted by an intron of 65 bp at position -6 upstream from the mature toxin. The protein sequence of this toxin was completely identical with that of a known A-type K+ current blocker BmTx3, belonging to scorpion alpha-KTx subfamily 15. Thus BmTx3 is the first reported alpha-KTx peptide also showing HERG-blocking activity, like gamma-KTx peptides. Moreover, different from classical alpha-KTx peptides, such as charybdotoxin, BmTx3 cannot block Shaker -type K+ channels. Phylogenetic tree analysis reveals that this toxin takes an intermediate position between classical alpha-KTx and gamma-KTx toxins. From a structural point of view, we propose that two separate functional faces might exist on the BmTx3 molecule, responsible for the two different K+-current-blocking functions. Face A, composed of Arg18 and Lys19 in the alpha-helix side, might correspond to HERG blocking activity, whereas Face B, containing a putative functional dyad (Lys27 and Tyr36) in the beta-sheet side, might correspond to A-type blocking activity. A specific deletion mutant with the disrupted Face B, BmTx3-Y36P37del, loses the A-type current-blocking activity, but keeps a similar HERG-blocking activity, as seen with the wild-type toxin.
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996, Pubmed,
Xenbase
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase Corona,
A large number of novel Ergtoxin-like genes and ERG K+-channels blocking peptides from scorpions of the genus Centruroides.
2002,
Pubmed Csank,
Nuclear pre-mRNA introns: analysis and comparison of intron sequences from Tetrahymena thermophila and other eukaryotes.
1990,
Pubmed Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed Dai,
Genomic organization of three novel toxins from the scorpion Buthus martensi Karsch that are active on potassium channels.
2000,
Pubmed Dauplais,
On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures.
1997,
Pubmed Delabre,
Promoter structure and intron-exon organization of a scorpion alpha-toxin gene.
1995,
Pubmed Ellis,
Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A).
2001,
Pubmed
,
Xenbase Goldstein,
The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.
1994,
Pubmed
,
Xenbase Goudet,
An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch.
2002,
Pubmed Gurevitz,
Diversification of neurotoxins by C-tail 'wiggling': a scorpion recipe for survival.
2001,
Pubmed Huys,
Purification, characterization and biosynthesis of parabutoxin 3, a component of Parabuthus transvaalicus venom.
2002,
Pubmed
,
Xenbase Korolkova,
New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.
2002,
Pubmed Kumar,
MEGA2: molecular evolutionary genetics analysis software.
2001,
Pubmed Legros,
Characterisation of the genes encoding Aa1 isoforms from the scorpion Androctonus australis.
2003,
Pubmed Legros,
Genomic organization of the KTX2 gene, encoding a 'short' scorpion toxin active on K+ channels.
1997,
Pubmed Pardo-Lopez,
Mapping the binding site of a human ether-a-go-go-related gene-specific peptide toxin (ErgTx) to the channel's outer vestibule.
2002,
Pubmed Park,
Design, synthesis, and functional expression of a gene for charybdotoxin, a peptide blocker of K+ channels.
1991,
Pubmed Peitsch,
Automated protein modelling--the proteome in 3D.
2000,
Pubmed Pisciotta,
The Androctonus australis garzoni scorpion venom contains toxins that selectively affect voltage-dependent K(+)-channels in cerebellum granular cells.
1998,
Pubmed Rauer,
Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca(2+)-activated over voltage-gated K(+) channels.
2000,
Pubmed Rodríguez de la Vega,
Novel interactions between K+ channels and scorpion toxins.
2003,
Pubmed Romi-Lebrun,
Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.
1997,
Pubmed
,
Xenbase Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase Srinivasan,
kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.
2002,
Pubmed Thompson,
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
1997,
Pubmed Tytgat,
Do voltage-gated Kv1.1 and inward rectifier Kir2.1 potassium channels form heteromultimers?
1996,
Pubmed
,
Xenbase Tytgat,
A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies.
1999,
Pubmed Vacher,
A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain.
2001,
Pubmed Vacher,
Expanding the scorpion toxin alpha-KTX 15 family with AmmTX3 from Androctonus mauretanicus.
2002,
Pubmed Vacher,
Functional consequences of deleting the two C-terminal residues of the scorpion toxin BmTX3.
2003,
Pubmed Wang,
Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis.
2003,
Pubmed Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed Wickenden,
K(+) channels as therapeutic drug targets.
2002,
Pubmed Wu,
Genomic organization of three neurotoxins active on small conductance Ca2+-activated potassium channels from the scorpion Buthus martensi Karsch.
1999,
Pubmed Wu,
The gene cloning and sequencing of Bm-12, a chlorotoxin-like peptide from the scorpion Buthus martensi Karsch.
2000,
Pubmed Xu,
Turret and pore block of K+ channels: what is the difference?
2003,
Pubmed Zhang,
BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1.
2003,
Pubmed
,
Xenbase
