7CSS

Solution structure of the topological isomer of Heat-stable enterotoxin produced by Enterotoxigenic Escherichia coli

7CSS の概要

• エントリーDOI: 10.2210/pdb7css/pdb
• 分子名称: CYS-CYS-GLU-LEU-CYS-CYS-ASN-PRO-ALA-CYS-THR-GLY-CYS (1 entity in total)
• 機能のキーワード: heat-stable enterotoxin, topological isomer, sth, sth(6-18), toxin
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1319.60

構造登録者

Shimamoto, S.,Hidaka, Y. (登録日: 2020-08-17, 公開日: 2020-12-16, 最終更新日: 2024-11-20)

主引用文献

Shimamoto, S.,Fukutsuji, M.,Osumi, T.,Goto, M.,Toyoda, H.,Hidaka, Y.
Topological Regulation of the Bioactive Conformation of a Disulfide-Rich Peptide, Heat-Stable Enterotoxin.
Molecules, 25:-, 2020

PubMed Abstract: Heat-stable enterotoxin (ST) produced by enterotoxigenic causes acute diarrhea and also can be used as a specific probe for colorectal cancer cells. ST contains three intra-molecular disulfide bonds (C1-C4, C2-C5, and C3-C6 connectivity). The chemical synthesis of ST provided not only the native type of ST but also a topological isomer that had the native disulfide pairings. Interestingly, the activity of the topological isomer was approximately 1/10-1/2 that of the native ST. To further investigate the bioactive conformation of this molecule and the regulation of disulfide-coupled folding during its chemical syntheses, we examined the folding mechanism of ST that occurs during its chemical synthesis. The folding intermediate of ST with two disulfide bonds (C1-C4 and C3-C6) and two Cys(Acm) residues, the precursor peptide, was treated with iodine to produce a third disulfide bond under several conditions. The topological isomer was predominantly produced under all conditions tested, along with trace amounts of the native type of ST. In addition, NMR measurements indicated that the topological isomer has a left-handed spiral structure similar to that of the precursor peptide, while the native type of ST had a right-handed spiral structure. These results indicate that the order of the regioselective formation of disulfide bonds is important for the regulation of the final conformation of disulfide-rich peptides in chemical synthesis.

PubMed: 33096591
DOI: 10.3390/molecules25204798

実験手法

SOLUTION NMR