Tumor marker disaccharide D-Gal-beta 1, 3-GalNAc complexed to heat-labile enterotoxin from Escherichia coli.
Heat-labile enterotoxin (LT) is part of the cholera toxin (CT) family and consists of a catalytic A subunit and a B pentamer that serves to recognize the oligosaccharide part of the GM1 ganglioside receptor. We report here the crystal structure of heat-labile enterotoxin in complex with the disaccharide portion of the Thomsen-Friedenreich (T-antigen) tumor marker. The toxin:carbohydrate complex is determined to 2.13 A resolution, yielding an R-factor of 18.5%. The T-antigen disaccharide, D-Gal-beta 1,3-GalNAc-Ser/Thr, is present in more than 85% of human carcinomas and monitoring its autoimmune response is used for the early detection of tumors. Insight into the molecular recognition of this tumor antigen by sugar binding proteins can benefit the development of a diagnostic tool for human carcinomas as well as a T-antigen directed anticancer drug delivery system.
van den Akker
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Department of Biochemistry, University of Washington, Seattle 98195, USA.
Steensma
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Hol
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WG
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D002772:Cholera Toxin / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D006358:Hot Temperature; D006801:Humans; D008968:Molecular Conformation
D015295:Antigens, Tumor-Associated, Carbohydrate; D001427:Bacterial Toxins; D014408:Biomarkers, Tumor; D004187:Disaccharides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C016467:Thomsen-Friedenreich antigen; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli