Solution structure of BmP08, a novel short-chain scorpion toxin from Buthus martensi Karsch.
A novel short-chain scorpion toxin BmP08 was purified from the venom of the Chinese scorpion Buthus martensi Karsch by a combination of gel-filtration, ion exchange, and reversed-phase chromatography. The primary sequence of BmP08 was determined using the tandem MS/MS technique and Edman degradation, as well as results of NMR sequential assignments. It is composed of 31 amino acid residues including six cysteine residues and shares less than 25% sequence identity with the known alpha-KTx toxins. BmP08 shows no inhibitory activity on all tested voltage-dependent and Ca(2+)-activated potassium channels. The 3D-structure of BmP08 has been determined by 2D-NMR spectroscopy and molecular modeling techniques. This toxin adopts a common alpha/beta-motif, but shows a distinctive local conformation and features a 3(10)-helix and a shorter beta-sheet. The unique structure is closely related to the distinct primary sequence of the toxin, especially to the novel arrangement of S-S linkages in the molecule, in which two disulfide bridges (C(i)-C(j) and C(i+3)-C(j+3)) link covalently the 3(10)-helix with one strand of the beta-sheet structure. The electrostatic potential surface analysis of the toxin reveals salt bridges and hydrogen bonds between the basic residues and negatively charged residues nearby in BmP08, which may be unfavorable for its binding with the known voltage-dependent and Ca(2+)-activated potassium channels. Thus, finding the target for this toxin should be an interesting task in the future.
Chen
Xiang
X
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, People's Republic of China.
Li
Yiming
Y
Tong
Xiaotian
X
Zhang
Naixia
N
Wu
Gong
G
Zhang
Qi
Q
Wu
Houming
H
D000595:Amino Acid Sequence; D000818:Animals; D002845:Chromatography; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry*; D012996:Solutions
C501658:P08 peptide, Buthus martensi; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D012996:Solutions