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The gastric pathogen Helicobacter pylori is a major cause of acute chronic gastritis and the development of stomach and duodenal ulcers. Chronic infection furthermore pre-disposes to the development of gastric cancer. Crucial to H. pylori survival within the hostile environment of the digestive system are the adhesins SabA and BabA; these molecules belong to the same protein family and permit the bacteria to bind tightly to sugar moieties LewisB and sialyl-LewisX, respectively, on the surface of epithelial cells lining the stomach and duodenum. Currently, no representative SabA / BabA structure has been determined, however, hampering the development of strategies to eliminate persistent H. pylori infections that fail to respond to conventional therapy. Here, using X-ray crystallography, we show that the soluble extracellular adhesin domain of SabA shares distant similarity to the tetratricopeptide repeat (TPR) fold family. The molecule broadly resembles a golf putter in shape, with the head region featuring a large cavity surrounded by loops that vary in sequence between different H. pylori strains. The N-terminal and C-terminal helices protrude at right angles from the head domain and together form a shaft that connects to a predicted outer membrane protein (OMP)-like beta-barrel trans-membrane domain. Using surface plasmon resonance, we were able to detect binding of the SabA adhesin domain to sialyl-LewisX and LewisX but not to LewisA, LewisB or LewisY. Substitution of the highly conserved glutamine residue 159 in the predicted ligand-binding pocket abrogates the binding of the SabA adhesin domain to sialyl-LewisX and LewisX. Taken together, these data suggest that the adhesin domain of SabA is sufficient in isolation for specific ligand binding.