1988 Fiscal Year Final Research Report Summary
Studies of the Tertiary Structure and Structural Requirements for Toxic Expression of Heat-stable Enterotoxins Produced by Enterotoxigenic Escherichia coli
| Project/Area Number |
62470022
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
有機化学一般
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| Research Institution | Osaka University |
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Principal Investigator |
SHIMONISHI Yasutsugu Institute for Protein Research, Osaka University, 蛋白質研究所, 教授 (00029951)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Enterotoxigenic Escherichia coli / Heat-stable enterotoxin / Disulfide linkages / Long-acting agonist / 毒性発現構造 |
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| Research Abstract |
Heat-stable enterotoxin (ST) produced by enterotoxigenic Escherichia coli causes acute diarrhea in human. Previously, we and others determined the amino acid sequences of the STs of enterotoxigenic E. coli, which consist of 19 and 18 residues. The present work was carried out with the aim to elucidate the tertiary structure of ST and the structural requirement for expression of its toxicity. The following tesults were obtained: 1) The positions of three intramolecular disulfide linkages not only in two STs of enterotoxigenic E. coli but also in sTs of yersinia entero colitica and vibrio cholerae non-01 were determined. The mode of disulfide linkages were same in all of the STs examined. 2) Analogs of the ST of enterotoxigenic E. coli with one or two among three disulfide linkages were synthesized and their activities were examined, demonstrating tha the special one of three disulfide linkages was essential for expression of the toxicity of the ST. 3) Analogs of STp (ST produced by a porcine stratin of enterotoxigenic E. coli) replaced by D-amino acid residues at a single position were synthesized. The analog of STp with D-Cys at position 5 had the same activity as that of STp and moreover the toxicity of the analog lasted after its administration into suckling mouse more than 24 hours, while the toxicity of STp decreased after 6-10 hours.
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