The role of 9-th position on the conformational construction of Heat-stable enterotoxin

摘要

The role of 9-th position on the conformational construction of porcine heat-stable enterotoxin analog (STp(5-17) ) was investigated. STp(5-17) analog of which Cys~6 and Cys~(14) were replaced by acetamidomethyl-L-Cys (Acm-Cys) and Cys~9 by D-Cys ([Acm-Cys~6, D-Cys~9, Acm-Cys~(14)] STp(5-17)) was used to form the disulfide bond selectively between Cys~6 and Cys~(14). [D-Cys~9] STp(5-17) with the similar toxicity to the native STp was formed by the I_2-oxidation of [Acm-Cys~6, D-Cys~9, Acm-Cys~(14)] STp(5-17). However, the native type of STp(5-17) has not been obtained from ([Acm-Cys~6, Acm-Cys~(14)] STp(5-17) via I_2-oxidation(2). Conformational analysis of [D-Cys~9] STp(5-17) by NMR method showed that this analog possessed the almost same conformation as that of STp(5-17). This finding indicates that D-Cys~9 in [Acm-Cys~6, D-Cys~9, Acm-Cys~(14)] STp(5-17) can take the a_L-torsion (left-handed a helices) to result in the formation of the native type conformer of [D-Cys~9] STp(5-17). Results in thisstudy demonstrates that taking the specific torsion at 9-th Cys is important factor to form the disulfide bond between Cys~6 and Cys~(14) giving the native type conformer.