BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents

	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
刊名	BIOCHEMICAL JOURNAL
	2004
卷号	378 期号:1 页码:745-752
关键词	Buthus martensi Karsch gene cloning phylogenetic tree potassium channel structure modelling scorpion toxin
通讯作者	Tytgat, J (reprint author), Univ Leuven, Toxicol Lab, Fac Pharmaceut Sci, E Van Evenstr 4, B-3000 Louvain, Belgium.,Jan.Tytgat@pharm.kuleuven.ac.be
英文摘要	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 a-KTx peptide also showing HERG-blocking activity, like gamma-KTx peptides. Moreover, different from classical a-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 Arg(18) and Lys(19) in the a-helix side, might correspond to HERG blocking activity, whereas Face 13, containing a putative functional dyad (Lys(27) and Tyr(36)) in the P-sheet side, might correspond to A-type blocking activity. A specific deletion mutant with the disrupted Face 13, BmTx3-Y36P37del, loses the A-type current-blocking activity, but keeps a similar HERG-blocking activity, as seen with the wild-type toxin.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	BUTHUS-MARTENSI KARSCH ; POTASSIUM CHANNEL ; GENOMIC ORGANIZATION ; ANDROCTONUS-AUSTRALIS ; CARDIAC-ARRHYTHMIA ; BINDING-SITE ; GENE ; PEPTIDE ; CHARYBDOTOXIN ; RESIDUES
收录类别	SCI
语种	英语
WOS记录号	WOS:000220481100005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2208]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Huys, I,Xu, CQ,Wang, CZ,et al. BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents[J]. BIOCHEMICAL JOURNAL,2004,378(1):745-752.
APA	Huys, I.,Xu, CQ.,Wang, CZ.,Vacher, H.,Martin-Eauclaire, MF.,...&Tytgat, J.(2004).BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.BIOCHEMICAL JOURNAL,378(1),745-752.
MLA	Huys, I,et al."BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents".BIOCHEMICAL JOURNAL 378.1(2004):745-752.