Comparison of the structural stability of two homologous toxins isolated from the Taiwan cobra (Naja naja atra) venom.
Cardiotoxin analogue III (CTX III) and cobrotoxin (CBTX) isolated from the Taiwan cobra venom (Naja naja atra) are structurally homologous, small molecular weight, all-beta-sheet proteins, cross-linked by four disulfide bonds at identical positions. The conformational stabilities of these toxins are compared based on temperature-dependent chemical shifts and amide proton exchange kinetics using two-dimensional NMR spectroscopy. The structure of CTX III is found to be significantly more stable than that of CBTX. In both the toxins, beta-strand III appears to constitute the stability core. In CTX III, the stability of the triple-stranded beta-sheet domain is observed to be markedly higher than the double-stranded beta-sheet segment. In contrast, in CBTX, both structural domains (double- and triple-stranded beta-sheet domains) appear to contribute equally to the stability of the protein. Estimation of the free energy of exchange (Delta G(ex)) of residues in CBTX and CTX III reveals that the enhanced stability of the structure of CTX III stems from the strong interactions among the beta-strands constituting the triple-stranded beta-sheet domain and also the molecular forces bridging the residues at the N- and C-terminal ends of the molecule.
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan (R.O.C.), China.
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Sivaraman
T K
TK
Kumar
K W
KW
Hung
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C
Yu
D000818:Animals; D002942:Circular Dichroism; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry*; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry*; D003903:Deuterium; D017815:Elapidae; D006358:Hot Temperature; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D013816:Thermodynamics
D004179:Cobra Cardiotoxin Proteins; D003039:Cobra Neurotoxin Proteins; D012996:Solutions; C082202:cardiotoxin III, Naja naja atra; D003903:Deuterium