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Infection and Immunity, March 2006, p. 1984-1988, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1984-1988.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Structural Analysis of the Interaction between Shiga Toxin B Subunits and Linear Polymers Bearing Clustered Globotriose Residues

Miho Watanabe,1,2 Katsura Igai,1,3 Koji Matsuoka,4 Atsushi Miyagawa,4 Toshiyuki Watanabe,4 Ryohei Yanoshita,2 Yuji Samejima,2 Daiyo Terunuma,4 Yasuhiro Natori,1 and Kiyotaka Nishikawa1,3*

Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan,1 Bioresources Research Laboratory, The Institute of Medical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan,2 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan,3 Department of Functional Materials Science, Saitama University, 255 Shimookubo, Urawa-shi, Saitama 338-8570, Japan4

Received 28 September 2005/ Returned for modification 17 November 2005/ Accepted 9 December 2005

We previously developed linear polymers bearing clustered trisaccharides of globotriaosylceramide (Gb3) as orally applicable Shiga toxin (Stx) neutralizers. Here, using a Gb3 polymer with a short spacer tethering the trisaccharide to the core, we found that shortening the spacer length markedly reduced the binding affinity for Stx2 but not Stx1. Moreover, mutational analysis revealed that the essential binding sites of the terminal trisaccharides were completely different between Stx1 and Stx2. These results provide the molecular basis for the interaction between Stx B subunits and Gb3 polymers.


* Corresponding author. Mailing address: Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Phone: 81-3-3202-7181. Fax: 81-3-5273-3038. E-mail: knishika{at}ri.imcj.go.jp.

Editor: A. D. O'Brien


Infection and Immunity, March 2006, p. 1984-1988, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1984-1988.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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