Unexpected structure of a C. difficile toxin A ligand necessitates an annotation correction in a popular screening library.
The structure of the pentasaccharide S259-1 in the Consortium for Functional Glycomics was investigated using a variety of techniques. Surprisingly, the structure differs from the structure assumed from the previously established specificity of the human fucosyltransferase FUT-III used in the last step of chemoenzymatic synthesis. When presented with a tetrasaccharide substrate containing both type I and type II disaccharide moieties, the enzyme generates a pentasaccharide in which the type II moiety is preferentially fucosylated. The unexpected product generated by FUT-III in this case highlights the importance of performing detailed structural analysis on products generated by enzymes.
Department of Chemistry, Alberta Ingenuity Centre for Carbohydrate Science, University of Calgary, Calgary AB T2N1N4, Canada.
Ping
P
Zhang
Nahid
N
Razi
Luiz
L
Eugenio
Messele
M
Fentabil
Elena N
EN
Kitova
John S
JS
Klassen
David R
DR
Bundle
Kenneth K-S
KK
Ng
Chang-Chun
CC
Ling
D001427:Bacterial Toxins / Q000737:chemistry*; D016360:Clostridioides difficile / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D001427:Bacterial Toxins; D004768:Enterotoxins; D008024:Ligands; D009844:Oligosaccharides; D011994:Recombinant Proteins; C570647:S259-1; C041348:tcdA protein, Clostridium difficile; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase