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• W2046613999 abstract "Pyranose–furanose mutases are essential enzymes in the life cycle of a number of microorganisms, but are absent in mammalian systems, and hence represent novel targets for drug development. To date, all such mutases show preferential recognition of a single substrate (e.g., UDP-Gal). We report here the detailed structural characterization of the first bifunctional pyranose–furanose mutase, which recognizes both UDP-Gal and UDP-GalNAc. The enzyme under investigation (cjUNGM) is involved in the biosynthesis of capsular polysaccharides (CPSs) in Campylobacter jejuni 11168. These CPSs are known virulence factors that are required for adhesion and invasion of human epithelial cells. Using a combination of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics and CORCEMA-ST calculations, we have characterized the binding of the enzyme to both UDP-Galp and UDP-GalpNAc, and compared these interactions with those of a homologous monofunctional mutase enzyme from E. coli (ecUGM). These studies reveal that two arginines in cjUNGM, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to a GalfNAc-containing CPS. In ecUGM, these arginines are replaced with histidine and lysine, respectively, and this results in an enzyme that is selective for UDP-Gal. We propose that these changes in amino acids allow C. jejuni 11168 to produce suitable quantities of the sugar nucleotide substrate required for the assembly of a CPS containing GalfNAc, which is essential for viability." @default.
• W2046613999 created "2016-06-24" @default.
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• W2046613999 date "2013-12-02" @default.
• W2046613999 modified "2023-09-27" @default.
• W2046613999 title "Specificity of a UDP-GalNAc Pyranose-Furanose Mutase: A Potential Therapeutic Target for<i>Campylobacter jejuni</i>Infections" @default.
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• W2046613999 doi "https://doi.org/10.1002/cbic.201300653" @default.
• W2046613999 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24302429" @default.
• W2046613999 hasPublicationYear "2013" @default.
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