NMR Solution Structure of a Two-Disulfide Derivative of Charybdotoxin: Structural Evidence for Conservation of Scorpion Toxin /
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- 作者：Jianxing Song ; Bernard Gilquin ; Nadè ; ge Jamin ; Eugenia Drakopoulou ; Marc Guenneugues ; Marc Dauplais ; Claudio Vita ; and André ; Mé ; nez
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：April 1, 1997
- 年：1997
- 卷：36
- 期：13
- 页码：3760 - 3766
- 全文大小：239K
- 年卷期：v.36,no.13(April 1, 1997)
- ISSN：1520-4995
文摘
The 
/
scorpion fold consisting of a short -helix and-sheet is a structural motif commonto scorpion toxins, insect defensins, and plant 
-thionins thatinvariably contains three disulfides. CHABIIis a two-disulfide derivative of the scorpion toxin charybdotoxin(ChTX), chemically synthesized byinserting two L--aminobutyric acids in place of the twohalf-cystine residues involved in the disulfide13-33. This disulfide is one of the two disulfides which connectthe -helix to the -sheet. The solutionstructure of CHABII was determined at pH 6.3 and 5 
C using 2D NMRand simulated annealing from513 distance and 46 dihedral angle constraints. The NMR structureof CHABII is well-defined as judgedfrom the low value of the averaged backbone rms deviation between the30 lowest energy structures andthe energy-minimized mean structure (<rmsd> = 0.65 Å for theentire sequence and 0.48 Å for the segment3-36). Analysis and comparison of the solution structures ofCHABII and ChTX lead to the followingconclusions: (i) the fold of CHABII is similar to that of ChTX asindicated by the low value of theaveraged backbone atomic rms deviation between the 10 lowest energysolution structures of the twoproteins (1.44 Å); (ii) the packing of the hydrophobic core iswell-preserved, underlying the critical structuralrole of the hydrophobic interactions even for such a small andcysteine-rich protein as ChTX.
/ scorpion fold consisting of a short -helix and-sheet is a structural motif commonto scorpion toxins, insect defensins, and plant -thionins thatinvariably contains three disulfides. CHABIIis a two-disulfide derivative of the scorpion toxin charybdotoxin(ChTX), chemically synthesized byinserting two L--aminobutyric acids in place of the twohalf-cystine residues involved in the disulfide13-33. This disulfide is one of the two disulfides which connectthe -helix to the -sheet. The solutionstructure of CHABII was determined at pH 6.3 and 5 C using 2D NMRand simulated annealing from513 distance and 46 dihedral angle constraints. The NMR structureof CHABII is well-defined as judgedfrom the low value of the averaged backbone rms deviation between the30 lowest energy structures andthe energy-minimized mean structure (<rmsd> = 0.65 Å for theentire sequence and 0.48 Å for the segment3-36). Analysis and comparison of the solution structures ofCHABII and ChTX lead to the followingconclusions: (i) the fold of CHABII is similar to that of ChTX asindicated by the low value of theaveraged backbone atomic rms deviation between the 10 lowest energysolution structures of the twoproteins (1.44 Å); (ii) the packing of the hydrophobic core iswell-preserved, underlying the critical structuralrole of the hydrophobic interactions even for such a small andcysteine-rich protein as ChTX.