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J. Biol. Chem., Vol. 280, Issue 20, 19695-19703, May 20, 2005

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Novel Binding Epitope for Helicobacter pylori Found in Neolacto Carbohydrate Chains

STRUCTURE AND CROSS-BINDING PROPERTIES^*

Halina Miller-Podraza, Boel Lanne¶, Jonas Ångström, Susann Teneberg, Maan Abul Milh, Per-Åke Jovall, Hasse Karlsson, and Karl-Anders Karlsson

From the Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 40530 Göteborg, Sweden

Helicobacter pylori is a bacterium that colonizes the stomach of a majority of the global human population causing common gastric diseases like ulcers and cancer. It has an unusually complex pattern of binding to various host glycoconjugates including interaction with sialylated, sulfated, and fucosylated sequences. The present study describes an additional binding epitope comprising the neolacto internal sequence of GlcNAc3-Gal4GlcNAc. The binding was detected on TLC plates as an interaction with a seven-sugar ganglioside of rabbit thymus. The glycolipid was purified and characterized as Neu5Gc3Gal4GlcNAc3Gal4GlcNAc3-Gal4Glc1Cer with less than 10% of the fraction carrying a repeated lacto (type-1) core chain, Gal3Glc-NAc3Gal3GlcNAc. After stepwise chemical and enzymatic degradation and structural analysis of products the strongest binder was found to be the pentaglycosylceramide GlcNAc3Gal4GlcNAc3Gal4Glc1-Cer, whereas the hexa- and tetraglycosylceramides were less active, and the trihexosylceramide was inactive. Further studies revealed that the terminal GlcNAc of the pentaglycosylceramide may be exchanged for either GalNAc3, GalNAc3, or Gal3 without loss of the activity. Calculated minimum energy conformers of these four isoreceptors show a substantial topographical similarity suggesting that this binding is a result of a molecular mimicry. Although the glycoconjugate composition of human gastric epithelial cells is not known in detail it is proposed that repeating N-acetyllactosamine units of glycoconjugates may serve as bacterial attachment sites in the stomach.

Received for publication, November 9, 2004 , and in revised form, March 2, 2005.

^* This work was supported by Swedish Research Council Grant 06X-12628, the Swedish Cancer Foundation, Wilhelm and Martina Lundgrens Research Foundation, the Swedish Medical Society, the Adlerbertska Research Foundation, Ingabritt and Arne Lundberg Foundation, and Symbicom Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

^¶ Present address: AstraZeneca R&D, S-431 83 Mölndal, Sweden.

To whom correspondence should be addressed. Tel.: 46-31-773-3154; Fax: 46-31-416108; Email: Halina.Miller-Podraza{at}medkem.gu.se.

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				M. Kobayashi, H. Lee, J. Nakayama, and M. Fukuda Roles of gastric mucin-type O-glycans in the pathogenesis of Helicobacter pylori infection Glycobiology, May 1, 2009; 19(5): 453 - 461. [Abstract] [Full Text] [PDF]

				H. Miller-Podraza, K. Weikkolainen, T. Larsson, P. Linde, J. Helin, J. Natunen, and K.-A. Karlsson Helicobacter pylori binding to new glycans based on N-acetyllactosamine Glycobiology, April 1, 2009; 19(4): 399 - 407. [Abstract] [Full Text] [PDF]